Difference between revisions of "Acute myeloid leukemia"
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=Guidelines= | =Guidelines= | ||
==ASH== | ==ASH== | ||
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*'''2020:''' Sekeres et al. [https://ashpublications.org/bloodadvances/article/4/15/3528/461693/American-Society-of-Hematology-2020-guidelines-for American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults] | *'''2020:''' Sekeres et al. [https://ashpublications.org/bloodadvances/article/4/15/3528/461693/American-Society-of-Hematology-2020-guidelines-for American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults] | ||
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==ELN== | ==ELN== | ||
*'''2022:''' Döhner et al. [https://doi.org/10.1182/blood.2022016867 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN] | *'''2022:''' Döhner et al. [https://doi.org/10.1182/blood.2022016867 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN] | ||
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*'''2017:''' Döhner et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel] | *'''2017:''' Döhner et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel] | ||
*'''2010:''' Döhner et al. [https://doi.org/10.1182/blood-2009-07-235358 Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet] | *'''2010:''' Döhner et al. [https://doi.org/10.1182/blood-2009-07-235358 Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet] | ||
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==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
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*'''2020:''' Heuser et al. [https://doi.org/10.1016/j.annonc.2020.02.018 Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | *'''2020:''' Heuser et al. [https://doi.org/10.1016/j.annonc.2020.02.018 Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | ||
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===Older=== | ===Older=== | ||
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*'''2013:''' Fey et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Acute-Myeloblastic-Leukaemia-in-Adult-Patients Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | *'''2013:''' Fey et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Acute-Myeloblastic-Leukaemia-in-Adult-Patients Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | ||
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=="How I Treat"== | =="How I Treat"== | ||
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*'''2020:''' DeWolf & Tallman [https://doi.org/10.1182/blood.2019001982 How I treat relapsed or refractory AML] | *'''2020:''' DeWolf & Tallman [https://doi.org/10.1182/blood.2019001982 How I treat relapsed or refractory AML] | ||
*'''2020:''' DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. [https://doi.org/10.1182/blood.2019001239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31765470 PubMed] | *'''2020:''' DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. [https://doi.org/10.1182/blood.2019001239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31765470 PubMed] | ||
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*'''2015:''' Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015 May 21;125(21):3246-52. Epub 2015 Mar 16. [http://www.bloodjournal.org/content/125/21/3246.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25778528 PubMed] | *'''2015:''' Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015 May 21;125(21):3246-52. Epub 2015 Mar 16. [http://www.bloodjournal.org/content/125/21/3246.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25778528 PubMed] | ||
*'''2014:''' Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. [http://www.bloodjournal.org/content/125/5/767.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515963 PubMed] | *'''2014:''' Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. [http://www.bloodjournal.org/content/125/5/767.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515963 PubMed] | ||
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==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
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*[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia] | *[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia] | ||
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==Antifungal prophylaxis== | ==Antifungal prophylaxis== | ||
*'''2022:''' Stemler et al. [https://doi.org/10.1016/S2352-3026(22)00073-4 Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association] | *'''2022:''' Stemler et al. [https://doi.org/10.1016/S2352-3026(22)00073-4 Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association] | ||
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===Older=== | ===Older=== | ||
*'''2015:''' Halpern et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia] | *'''2015:''' Halpern et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia] | ||
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=Upfront induction therapy, standard and older "fit" patients= | =Upfront induction therapy, standard and older "fit" patients= | ||
''These are aggressive remission induction regimens given with curative intent.'' | ''These are aggressive remission induction regimens given with curative intent.'' | ||
==7+3d (standard-dose) {{#subobject:9f31ad|Regimen=1}}== | ==7+3d (standard-dose) {{#subobject:9f31ad|Regimen=1}}== | ||
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7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | ||
<br>AD: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>D</u>'''aunorubicin | <br>AD: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>D</u>'''aunorubicin | ||
<br>DA: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine) | <br>DA: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 700/135 (CI Ara-C) {{#subobject:bb27bc|Variant=1}}=== | ===Regimen variant #1, 700/135 (CI Ara-C) {{#subobject:bb27bc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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''Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.'' | ''Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
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'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
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*ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3i|7+3i]] | *ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3i|7+3i]] | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 700/150 (CI Ara-C) {{#subobject:9934a6|Variant=1}}=== | ===Regimen variant #2, 700/150 (CI Ara-C) {{#subobject:9934a6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | ||
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'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1120/120 (intermittent Ara-C) {{#subobject:1f1bb5|Variant=1}}=== | ===Regimen variant #3, 1120/120 (intermittent Ara-C) {{#subobject:1f1bb5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7 | *[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7 | ||
*[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | ||
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'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 1400/135 (CI Ara-C) {{#subobject:635ecb|Variant=1}}=== | ===Regimen variant #4, 1400/135 (CI Ara-C) {{#subobject:635ecb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
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'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
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*CALGB 9222: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus multi-agent [[Regimen_classes#Chemotherapy|chemotherapy]] consolidation | *CALGB 9222: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus multi-agent [[Regimen_classes#Chemotherapy|chemotherapy]] consolidation | ||
*HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation | *HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation | ||
*ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] if younger than 60 or [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] if greater than or equal to 60. | *ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] if younger than 60 or [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] if greater than or equal to 60. | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. [https://pubmed.ncbi.nlm.nih.gov/4586956 PubMed] | #Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. [https://pubmed.ncbi.nlm.nih.gov/4586956 PubMed] | ||
#'''CALGB 7421:''' Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. [http://www.bloodjournal.org/content/58/6/1203.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6946847 PubMed] | #'''CALGB 7421:''' Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. [http://www.bloodjournal.org/content/58/6/1203.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6946847 PubMed] | ||
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#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047 | #'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047 | ||
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed] | ##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed] | ||
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==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}== | ==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}== | ||
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7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}=== | ===Regimen variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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''Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.'' | ''Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
**Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5 | **Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5 | ||
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'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
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*AML2003: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus [[#MAC.2FMAMAC.2FMAC_99|MAC/MAMAC/MAC]] consolidation | *AML2003: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus [[#MAC.2FMAMAC.2FMAC_99|MAC/MAMAC/MAC]] consolidation | ||
*CALGB 10201: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2 | *CALGB 10201: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2 | ||
*SWOG S0106: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3 | *SWOG S0106: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3 | ||
*CLTR0310-301: [[#5.2B2d|5+2d]] consolidation | *CLTR0310-301: [[#5.2B2d|5+2d]] consolidation | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:cf53dd|Variant=1}}=== | ===Regimen variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:cf53dd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | ||
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====Supportive therapy==== | ====Supportive therapy==== | ||
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*"According to commonly accepted guidelines with no prophylactic IV antibiotics" | *"According to commonly accepted guidelines with no prophylactic IV antibiotics" | ||
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression | ||
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'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule. | *Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule. | ||
*PALG AML1/1999, non-responders: [[#CLAG|CLAG]] salvage | *PALG AML1/1999, non-responders: [[#CLAG|CLAG]] salvage | ||
*Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | *Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | ||
*ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation | *ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed] | #'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed] | ||
#'''LAM-2001:''' Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. [https://www.nature.com/articles/leu2010111 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20508614 PubMed] | #'''LAM-2001:''' Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. [https://www.nature.com/articles/leu2010111 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20508614 PubMed] | ||
Line 495: | Line 478: | ||
#'''ECOG E2906:''' NCT02085408 | #'''ECOG E2906:''' NCT02085408 | ||
#'''ENHANCE-2:''' NCT04778397 | #'''ENHANCE-2:''' NCT04778397 | ||
− | |||
==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}== | ==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}== | ||
− | |||
7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 700/270 {{#subobject:70583e|Variant=1}}=== | ===Regimen variant #1, 700/270 {{#subobject:70583e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 520: | Line 502: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*JHOC-J1101: Patients with residual leukemia at day 14 underwent [[#5.2B2d_2|5+2d]] salvage | *JHOC-J1101: Patients with residual leukemia at day 14 underwent [[#5.2B2d_2|5+2d]] salvage | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 1400/240 {{#subobject:a33bec|Variant=1}}=== | ===Regimen variant #2, 1400/240 {{#subobject:a33bec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 545: | Line 528: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1400/270 {{#subobject:664ec|Variant=1}}=== | ===Regimen variant #3, 1400/270 {{#subobject:664ec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 579: | Line 562: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation | *HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation | ||
*COSAH C-022, with CR, good- or intermediate-risk cytogenetics: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | *COSAH C-022, with CR, good- or intermediate-risk cytogenetics: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | ||
*COSAH C-022, with CR, high-risk cytogenetics: [[#Cytarabine_.26_Etoposide_88|Cytarabine & etoposide]] consolidation | *COSAH C-022, with CR, high-risk cytogenetics: [[#Cytarabine_.26_Etoposide_88|Cytarabine & etoposide]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA 9000:''' Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. [http://www.bloodjournal.org/content/104/8/2467.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15142880 PubMed] | #'''ALFA 9000:''' Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. [http://www.bloodjournal.org/content/104/8/2467.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15142880 PubMed] | ||
#'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377 | #'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377 | ||
Line 600: | Line 582: | ||
#'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972 | #'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972 | ||
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | ||
− | |||
==7+3d & GO {{#subobject:869f84|Regimen=1}}== | ==7+3d & GO {{#subobject:869f84|Regimen=1}}== | ||
− | |||
7+3d & GO: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | 7+3d & GO: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, split GO dosing {{#subobject:4c0a05|Variant=1}}=== | ===Regimen variant #1, split GO dosing {{#subobject:4c0a05|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 619: | Line 600: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients in CR or CRp and platelet count at least 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine.2C_Daunorubicin.2C_Gemtuzumab_ozogamicin|Cytarabine, Daunorubicin, Gemtuzumab ozogamicin]] consolidation | *Patients in CR or CRp and platelet count at least 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine.2C_Daunorubicin.2C_Gemtuzumab_ozogamicin|Cytarabine, Daunorubicin, Gemtuzumab ozogamicin]] consolidation | ||
*Patients in CR or CRp and platelet count less than 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin]] consolidation | *Patients in CR or CRp and platelet count less than 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin]] consolidation | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, single-day GO {{#subobject:4ug8f5|Variant=1}}=== | ===Regimen variant #2, single-day GO {{#subobject:4ug8f5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 650: | Line 630: | ||
|} | |} | ||
''Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.'' | ''Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV over 2 hours once on day 4 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV over 2 hours once on day 4 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3 | *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3 | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | ||
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ||
#'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709 | #'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709 | ||
− | |||
==7+3i {{#subobject:717935|Regimen=1}}== | ==7+3i {{#subobject:717935|Regimen=1}}== | ||
− | |||
7+3i: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin | 7+3i: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin | ||
<br>AI: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>I</u>'''darubicin | <br>AI: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>I</u>'''darubicin | ||
<br>IA: '''<u>I</u>'''darubicin & '''<u>A</u>'''ra-C (Cytarabine) | <br>IA: '''<u>I</u>'''darubicin & '''<u>A</u>'''ra-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 80/12, intermittent Ara-C {{#subobject:bdc11c|Variant=1}}=== | ===Regimen variant #1, 80/12, intermittent Ara-C {{#subobject:bdc11c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 690: | Line 666: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7 | *[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7 | ||
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 100/12, CI Ara-C {{#subobject:c6cda|Variant=1}}=== | ===Regimen variant #2, 100/12, CI Ara-C {{#subobject:c6cda|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 748: | Line 724: | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | + | '''7-day course (see note)''' | |
− | '''7-day course''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
===Regimen variant #3, 100/13, CI Ara-C {{#subobject:7f2eec|Variant=1}}=== | ===Regimen variant #3, 100/13, CI Ara-C {{#subobject:7f2eec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 772: | Line 747: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 13 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 13 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 200/12, CI Ara-C {{#subobject:f33de6|Variant=1}}=== | ===Regimen variant #4, 200/12, CI Ara-C {{#subobject:f33de6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 824: | Line 799: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3 | ||
**Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7 | **Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*HOVON/SAKK AML 29 & AML 42: [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]] | *HOVON/SAKK AML 29 & AML 42: [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]] | ||
*ALFA-9801, patients achieiving CR: [[#Cytarabine_.26_Idarubicin_2|cytarabine & idarubicin]] consolidation | *ALFA-9801, patients achieiving CR: [[#Cytarabine_.26_Idarubicin_2|cytarabine & idarubicin]] consolidation | ||
Line 838: | Line 813: | ||
*COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE]] consolidation | *COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE]] consolidation | ||
*HOVON/SAKK-132: [[#Daunorubicin_.26_IDAC|Daunorubicin & IDAC]] (remission induction cycle II) | *HOVON/SAKK-132: [[#Daunorubicin_.26_IDAC|Daunorubicin & IDAC]] (remission induction cycle II) | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, with range {{#subobject:eb0168|Variant=1}}=== | ===Regimen variant #5, with range {{#subobject:eb0168|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 854: | Line 830: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 to 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 to 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 9 to 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 9 to 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. [https://www.ejcancer.com/article/0277-5379(91)90181-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/1829918 PubMed] | #Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. [https://www.ejcancer.com/article/0277-5379(91)90181-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/1829918 PubMed] | ||
#Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1730080 PubMed] | #Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1730080 PubMed] | ||
Line 880: | Line 855: | ||
# '''HOVON/SAKK-132:''' Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. [https://doi.org/10.1182/bloodadvances.2020003855 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7903238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33616652/ PubMed] | # '''HOVON/SAKK-132:''' Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. [https://doi.org/10.1182/bloodadvances.2020003855 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7903238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33616652/ PubMed] | ||
# '''SWOG S1203:''' NCT01802333 | # '''SWOG S1203:''' NCT01802333 | ||
− | |||
==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}== | ==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:567ab9|Variant=1}}=== | ===Regimen {{#subobject:567ab9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 896: | Line 869: | ||
|} | |} | ||
''Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.'' | ''Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] by the following age-based criteria: | *[[Cytarabine (Ara-C)]] by the following age-based criteria: | ||
**60 and younger: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m<sup>2</sup>) | **60 and younger: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m<sup>2</sup>) | ||
**Older than 60: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m<sup>2</sup>) | **Older than 60: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 7 | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 7 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib]] consolidation | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | ||
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ||
− | |||
==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}== | ==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:0e6b97|Variant=1}}=== | ===Regimen {{#subobject:0e6b97|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 933: | Line 901: | ||
|} | |} | ||
''Note: glasdegib is continued beyond induction; see paper for details.'' | ''Note: glasdegib is continued beyond induction; see paper for details.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Glasdegib (Daurismo)]] 100 mg PO once per day, started on day -3 | *[[Glasdegib (Daurismo)]] 100 mg PO once per day, started on day -3 | ||
− | |||
'''28-day course''' | '''28-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation | *[[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''B1371003:''' Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. [https://doi.org/10.1002/ajh.25238 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30074259 PubMed] NCT01546038 | #'''B1371003:''' Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. [https://doi.org/10.1002/ajh.25238 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30074259 PubMed] NCT01546038 | ||
− | |||
==7+3m {{#subobject:240c72|Regimen=1}}== | ==7+3m {{#subobject:240c72|Regimen=1}}== | ||
− | |||
7+3m: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>m</u>'''itoxantrone | 7+3m: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>m</u>'''itoxantrone | ||
<br>MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:7d87af|Variant=1}}=== | ===Regimen {{#subobject:7d87af|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 976: | Line 940: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3m|7+3m]] | *Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3m|7+3m]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. [https://pubmed.ncbi.nlm.nih.gov/2179638 PubMed] | #Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. [https://pubmed.ncbi.nlm.nih.gov/2179638 PubMed] | ||
#'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052 | #'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052 | ||
− | |||
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}== | ==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}== | ||
− | |||
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ||
<br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide | <br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide | ||
<br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | <br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | ||
<br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | <br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 7-3-7, 700/150/525 {{#subobject:386fd2|Variant=1}}=== | ===Regimen variant #1, 7-3-7, 700/150/525 {{#subobject:386fd2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,012: | Line 974: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7 | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7 | ||
− | |||
'''7-day course; can be repeated up to 3 times if CR not achieved''' | '''7-day course; can be repeated up to 3 times if CR not achieved''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*5-2-5 consolidation x 2 | *5-2-5 consolidation x 2 | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 7-3-3, 700/180/300 {{#subobject:31dcd2|Variant=1}}=== | ===Regimen variant #2, 7-3-3, 700/180/300 {{#subobject:31dcd2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,038: | Line 1,001: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 7-3-3, 700/270/300 {{#subobject:3gh1d2|Variant=1}}=== | ===Regimen variant #3, 7-3-3, 700/270/300 {{#subobject:3gh1d2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,061: | Line 1,024: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C {{#subobject:7ce6f9|Variant=1}}=== | ===Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C {{#subobject:7ce6f9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,084: | Line 1,047: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days, started on day 1 (total dose: 1000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days, started on day 1 (total dose: 1000 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C {{#subobject:7ce6f9|Variant=1}}=== | ===Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C {{#subobject:7ce6f9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,107: | Line 1,070: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 25 mg/m<sup>2</sup>/day IV bolus once on day 1, then 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days (total dose: 1025 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 25 mg/m<sup>2</sup>/day IV bolus once on day 1, then 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days (total dose: 1025 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}=== | ===Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,137: | Line 1,100: | ||
|} | |} | ||
''Note: these trials have complicated treatment schemas; see papers for details.'' | ''Note: these trials have complicated treatment schemas; see papers for details.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction | *UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8 | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
'''8-day course''' | '''8-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*UK MRC AML10: MACE consolidation | *UK MRC AML10: MACE consolidation | ||
*UK MRC AML15: Consolidation (see paper for details) | *UK MRC AML15: Consolidation (see paper for details) | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}=== | ===Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,178: | Line 1,145: | ||
|} | |} | ||
''Note: these trials have complicated treatment schemas; see papers for details.'' | ''Note: these trials have complicated treatment schemas; see papers for details.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10 | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction | *[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed] | #Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed] | ||
#'''UK MRC AML10:''' Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed] | #'''UK MRC AML10:''' Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed] | ||
Line 1,206: | Line 1,172: | ||
<!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. --> | <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. --> | ||
#'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128 | #'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128 | ||
− | |||
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}== | ==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}== | ||
− | |||
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ||
<br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | <br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide | ||
<br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide | <br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, HIDAC-3-5 {{#subobject:b1a101|Variant=1}}=== | ===Regimen variant #1, HIDAC-3-5 {{#subobject:b1a101|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,227: | Line 1,192: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, HIDAC-3-7 {{#subobject:386df8|Variant=1}}=== | ===Regimen variant #2, HIDAC-3-7 {{#subobject:386df8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,250: | Line 1,215: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7 | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7 | ||
− | |||
'''7-day course; can be repeated up to 3 times if CR not achieved''' | '''7-day course; can be repeated up to 3 times if CR not achieved''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*5-2-5 consolidation x 2 | *5-2-5 consolidation x 2 | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed] | #Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed] | ||
<!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. --> | <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. --> | ||
#'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128 | #'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128 | ||
− | |||
==AIE {{#subobject:948b49|Regimen=1}}== | ==AIE {{#subobject:948b49|Regimen=1}}== | ||
− | |||
AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide | AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide | ||
<br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide | <br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:c7b35a|Variant=1}}=== | ===Regimen {{#subobject:c7b35a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,310: | Line 1,273: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*ALLG M7: ICE versus IcE consolidation | *ALLG M7: ICE versus IcE consolidation | ||
*NILG AML 02/06, early CR: IC consolidation | *NILG AML 02/06, early CR: IC consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALLG M7:''' Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. [http://www.bloodjournal.org/content/105/2/481.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15213095 PubMed] | #'''ALLG M7:''' Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. [http://www.bloodjournal.org/content/105/2/481.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15213095 PubMed] | ||
#Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. [https://www.nature.com/articles/2403528 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15385923 PubMed] | #Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. [https://www.nature.com/articles/2403528 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15385923 PubMed] | ||
Line 1,329: | Line 1,291: | ||
#'''CRIANT:''' de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellström-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. Epub 2010 May 21. [http://www.haematologica.org/content/95/10/1754.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20494931 PubMed] NCT00002926 | #'''CRIANT:''' de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellström-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. Epub 2010 May 21. [http://www.haematologica.org/content/95/10/1754.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20494931 PubMed] NCT00002926 | ||
#'''NILG AML 02/06:''' Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. [http://www.bloodadvances.org/content/3/7/1103.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30948365 PubMed] NCT00495287 | #'''NILG AML 02/06:''' Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. [http://www.bloodadvances.org/content/3/7/1103.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30948365 PubMed] NCT00495287 | ||
− | |||
==CIA {{#subobject:de6dec|Regimen=1}}== | ==CIA {{#subobject:de6dec|Regimen=1}}== | ||
− | |||
CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine) | CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}=== | ===Regimen variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,348: | Line 1,309: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given 4 hours before cytarabine''' | *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given 4 hours before cytarabine''' | ||
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients not achieving CR or CRp: Optional second [[#CIA|CIA]] induction | *Patients not achieving CR or CRp: Optional second [[#CIA|CIA]] induction | ||
*Patients achieving CR or CRp: [[#CIA_2|CIA]] consolidation | *Patients achieving CR or CRp: [[#CIA_2|CIA]] consolidation | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 20/10/1000 {{#subobject:4a7d81|Variant=1}}=== | ===Regimen variant #2, 20/10/1000 {{#subobject:4a7d81|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,371: | Line 1,333: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*[[Levofloxacin (Levaquin)]] | *[[Levofloxacin (Levaquin)]] | ||
*[[Itraconazole (Sporanox)]] | *[[Itraconazole (Sporanox)]] | ||
*[[Valacyclovir (Valtrex)]] | *[[Valacyclovir (Valtrex)]] | ||
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with PR: a second course with the same drugs, doses, and schedule. | *Patients with PR: a second course with the same drugs, doses, and schedule. | ||
*Patients achieving CR or CRi: [[#CIA_2|CIA]] consolidation | *Patients achieving CR or CRi: [[#CIA_2|CIA]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed] | #Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed] | ||
#'''MDACC 2010-0788:''' Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. [https://doi.org/10.1002/cncr.30883 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28708931 PubMed] NCT01289457 | #'''MDACC 2010-0788:''' Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. [https://doi.org/10.1002/cncr.30883 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28708931 PubMed] NCT01289457 | ||
− | |||
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}== | ==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}== | ||
− | |||
DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine | DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}=== | ===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,420: | Line 1,378: | ||
|} | |} | ||
''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.'' | ''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*See papers for details (to be completed). | *See papers for details (to be completed). | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 60 mg/m<sup>2</sup> dauno {{#subobject:211741|Variant=1}}=== | ===Regimen variant #2, 60 mg/m<sup>2</sup> dauno {{#subobject:211741|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,446: | Line 1,405: | ||
|} | |} | ||
''Note: this regimen is very similar to [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.'' | ''Note: this regimen is very similar to [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*CBF: [[#DA_3.2B8_.26_GO|DA 3+8 & GO]] | *CBF: [[#DA_3.2B8_.26_GO|DA 3+8 & GO]] | ||
*Non-CBF, no FLT3 mutation, not poor risk: [[#DA_3.2B8|DA 3+8]] versus DA 3+8 & Everolimus | *Non-CBF, no FLT3 mutation, not poor risk: [[#DA_3.2B8|DA 3+8]] versus DA 3+8 & Everolimus | ||
*Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus [[#FLAG-Ida_2|FLAG-Ida]] | *Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus [[#FLAG-Ida_2|FLAG-Ida]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | ||
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ||
Line 1,467: | Line 1,426: | ||
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | ||
##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed] | ##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed] | ||
− | |||
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}== | ==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}== | ||
− | |||
DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6a938e|Variant=1}}=== | ===Regimen {{#subobject:6a938e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,492: | Line 1,450: | ||
|- | |- | ||
|} | |} | ||
− | ''Both trials have complicated treatment schemas; see papers for details.'' | + | ''Note: Both trials have complicated treatment schemas; see papers for details.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10 | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*See paper for details (to be completed). | *See paper for details (to be completed). | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | ||
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ||
Line 1,515: | Line 1,470: | ||
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed] | ##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed] | ||
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed] | ##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed] | ||
− | |||
==DAC {{#subobject:9b1553|Regimen=1}}== | ==DAC {{#subobject:9b1553|Regimen=1}}== | ||
− | |||
DAC: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''ladribine | DAC: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''ladribine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:f00b8a|Variant=1}}=== | ===Regimen {{#subobject:f00b8a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,543: | Line 1,497: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>) | ||
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5 | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*"According to commonly accepted guidelines with no prophylactic IV antibiotics" | *"According to commonly accepted guidelines with no prophylactic IV antibiotics" | ||
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with only partial remission in both studies underwent a second course with the same drugs, doses, and schedule. | *Patients with only partial remission in both studies underwent a second course with the same drugs, doses, and schedule. | ||
*Non-responders in PALG AML1/1999: [[#CLAG|CLAG]] salvage | *Non-responders in PALG AML1/1999: [[#CLAG|CLAG]] salvage | ||
*Patients in remission in both studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | *Patients in remission in both studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed] | #'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed] | ||
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed] | #'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed] | ||
− | |||
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}== | ==FLAG-Ida {{#subobject:7fc219|Regimen=1}}== | ||
− | |||
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin | FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:44e85e|Variant=1}}=== | ===Regimen {{#subobject:44e85e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,585: | Line 1,535: | ||
|} | |} | ||
''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.'' | ''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6 | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine''' | ||
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6 | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6 | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7 | *[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*See paper for details | *See paper for details | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961 | ||
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed] | ||
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed] | ##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed] | ||
− | |||
==HAA {{#subobject:0788e0|Regimen=1}}== | ==HAA {{#subobject:0788e0|Regimen=1}}== | ||
− | |||
HAA: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>A</u>'''clarubicin | HAA: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>A</u>'''clarubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5c5c2e|Variant=1}}=== | ===Regimen {{#subobject:5c5c2e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,628: | Line 1,574: | ||
|} | |} | ||
''Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.'' | ''Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Omacetaxine (Synribo)]] 2 mg/m<sup>2</sup>/day (route not specified) on days 1 to 7 | *[[Omacetaxine (Synribo)]] 2 mg/m<sup>2</sup>/day (route not specified) on days 1 to 7 | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 7 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 7 | ||
*[[Aclarubicin (Aclacinon)]] 20 mg IV once per day on days 1 to 7 | *[[Aclarubicin (Aclacinon)]] 20 mg IV once per day on days 1 to 7 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*Patient in CR: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2 | *Patient in CR: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2 | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://doi.org/10.1016/S1470-2045(13)70152-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23664707 PubMed] ChiCTR-TRC-06000054 | #Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://doi.org/10.1016/S1470-2045(13)70152-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23664707 PubMed] ChiCTR-TRC-06000054 | ||
− | |||
==ICL {{#subobject:a904d7|Regimen=1}}== | ==ICL {{#subobject:a904d7|Regimen=1}}== | ||
− | |||
ICL: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>L</u>'''omustine | ICL: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>L</u>'''omustine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:909d7e|Variant=1}}=== | ===Regimen {{#subobject:909d7e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,658: | Line 1,604: | ||
| style="background-color:#91cf60" |Seems to have superior OS<br>OS24: 56% vs 48%<br>(HR 0.73, 95% CI 0.54-0.99) | | style="background-color:#91cf60" |Seems to have superior OS<br>OS24: 56% vs 48%<br>(HR 0.73, 95% CI 0.54-0.99) | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
*[[Lomustine (CCNU)]] 200 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 200 mg/m<sup>2</sup> PO once on day 1 | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Acute_myeloid_leukemia#IC_.26_Norethandrolone|IC and methotrexate/mercaptopurine with norethandrolone]] | *[[Acute_myeloid_leukemia#IC_.26_Norethandrolone|IC and methotrexate/mercaptopurine with norethandrolone]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''LAM-SA 2007:''' Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. [https://doi.org/10.1200/JCO.2018.78.7366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30260758 PubMed] NCT00590837 | #'''LAM-SA 2007:''' Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. [https://doi.org/10.1200/JCO.2018.78.7366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30260758 PubMed] NCT00590837 | ||
− | |||
==MEC {{#subobject:324735|Regimen=1}}== | ==MEC {{#subobject:324735|Regimen=1}}== | ||
− | |||
MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine | MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine | ||
<br>MICE: '''<u>MI</u>'''toxantrone, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide | <br>MICE: '''<u>MI</u>'''toxantrone, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide | ||
<br>MAE: '''<u>M</u>'''itoxantrone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>E</u>'''toposide | <br>MAE: '''<u>M</u>'''itoxantrone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:33e408|Variant=1}}=== | ===Regimen {{#subobject:33e408|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,699: | Line 1,643: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 7 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Mitoxantrone (Novantrone)]] 7 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>) | ||
− | |||
'''7-day course''' | '''7-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''EORTC/GIMEMA AML-13:''' Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. [http://www.bloodjournal.org/content/106/1/27.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895135/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15761020 PubMed] NCT00002719 | #'''EORTC/GIMEMA AML-13:''' Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. [http://www.bloodjournal.org/content/106/1/27.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895135/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15761020 PubMed] NCT00002719 | ||
##'''Update:''' Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. [https://www.nature.com/articles/2404356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16932345 PubMed] | ##'''Update:''' Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. [https://www.nature.com/articles/2404356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16932345 PubMed] | ||
#'''EORTC/GIMEMA AML-17:''' Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. [https://doi.org/10.1200/JCO.2013.49.0771 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24127442 PubMed] NCT00052299 | #'''EORTC/GIMEMA AML-17:''' Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. [https://doi.org/10.1200/JCO.2013.49.0771 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24127442 PubMed] NCT00052299 | ||
− | |||
=Subsequent induction therapy, standard and older "fit" patients= | =Subsequent induction therapy, standard and older "fit" patients= | ||
''Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.'' | ''Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.'' | ||
− | |||
==DA 3+8 {{#subobject:5c6662|Regimen=1}}== | ==DA 3+8 {{#subobject:5c6662|Regimen=1}}== | ||
− | |||
DA 3+8: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine | DA 3+8: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:aq1641|Variant=1}}=== | ===Regimen {{#subobject:aq1641|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,734: | Line 1,674: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk | *Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose | *[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8 | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2 | *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2 | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | ||
##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed] | ##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed] | ||
− | |||
==DA 3+8 & GO {{#subobject:6yy4bz|Regimen=1}}== | ==DA 3+8 & GO {{#subobject:6yy4bz|Regimen=1}}== | ||
− | |||
DA 3+8 & GO: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 8</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | DA 3+8 & GO: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 8</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6a51fv|Variant=1}}=== | ===Regimen {{#subobject:6a51fv|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,765: | Line 1,709: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*Core-binding factor (CBF) AML | *Core-binding factor (CBF) AML | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose | *[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8 | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''8-day course''' | '''8-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2 | *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2 | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535 | ||
Line 1,789: | Line 1,736: | ||
''Note: these regimens are generally considered to be part of a non-curative line of treatment.'' | ''Note: these regimens are generally considered to be part of a non-curative line of treatment.'' | ||
==Azacitidine monotherapy {{#subobject:791718|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:791718|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:7509ab|Variant=1}}=== | ===Regimen {{#subobject:7509ab|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,824: | Line 1,771: | ||
|} | |} | ||
''Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.'' | ''Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7 | ||
− | |||
'''28-day cycle for at least 6 cycles''' | '''28-day cycle for at least 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''AZA PH GL 2003:''' Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. [https://doi.org/10.1200/JCO.2009.23.8329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20026804 PubMed] NCT00071799 | #'''AZA PH GL 2003:''' Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. [https://doi.org/10.1200/JCO.2009.23.8329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20026804 PubMed] NCT00071799 | ||
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047 | #'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047 | ||
Line 1,839: | Line 1,784: | ||
# '''PEVOLAM:''' NCT04090736 | # '''PEVOLAM:''' NCT04090736 | ||
# '''PRAN-16-52:''' NCT03151408 | # '''PRAN-16-52:''' NCT03151408 | ||
− | |||
==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}== | ==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:1ea50d|Variant=1}}=== | ===Regimen {{#subobject:1ea50d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,863: | Line 1,807: | ||
|- | |- | ||
|} | |} | ||
− | ''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.'' | + | ''Note: Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Venetoclax (Venclexta)]] as follows: | *[[Venetoclax (Venclexta)]] as follows: | ||
**Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28 | **Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28 | ||
**Cycle 2 onwards: 400 mg PO once per day | **Cycle 2 onwards: 400 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773] | #'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773] | ||
##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed] | ##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed] | ||
#'''VIALE-A:''' DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. [https://doi.org/10.1056/nejmoa2012971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32786187 PubMed] NCT02993523 | #'''VIALE-A:''' DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. [https://doi.org/10.1056/nejmoa2012971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32786187 PubMed] NCT02993523 | ||
#'''ENHANCE-2:''' NCT04778397 | #'''ENHANCE-2:''' NCT04778397 | ||
− | |||
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}== | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Protocol {{#subobject:188f5c|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 1,901: | Line 1,839: | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.'' | |
− | ''Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |||
====Supportive therapy, pre-treatment phase==== | ====Supportive therapy, pre-treatment phase==== | ||
− | |||
*[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or in higher doses if necessary | *[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or in higher doses if necessary | ||
− | |||
''Once WBC is less than 10 x 10<sup>9</sup>/L, stop Hydrea and proceed:'' | ''Once WBC is less than 10 x 10<sup>9</sup>/L, stop Hydrea and proceed:'' | ||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | ||
− | |||
'''8-day course''' | '''8-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered | *If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered | ||
*Patients achieving CR or CRi: [[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine and gemtuzumab ozogamicin]] consolidation, within 60 days | *Patients achieving CR or CRi: [[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine and gemtuzumab ozogamicin]] consolidation, within 60 days | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [https://doi.org/10.1080/10428190802451254 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19021057 PubMed] | #Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [https://doi.org/10.1080/10428190802451254 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19021057 PubMed] | ||
<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | ||
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | ||
− | |||
==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}== | ==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 20 mg/m<sup>2</sup> {{#subobject:42be8e|Variant=1}}=== | ===Regimen variant #1, 20 mg/m<sup>2</sup> {{#subobject:42be8e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,952: | Line 1,879: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2013 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2013 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''4- to 6-week cycle for 4 cycles''' | '''4- to 6-week cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f9ef00|Variant=1}}=== | ===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f9ef00|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,985: | Line 1,912: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*A second induction was permitted for SD or better. | *A second induction was permitted for SD or better. | ||
*MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation | *MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218 | #'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218 | ||
#'''UWCM-001; BIOV-121:''' Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. [https://doi.org/10.1200/JCO.2009.26.4242 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20385984 PubMed] | #'''UWCM-001; BIOV-121:''' Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. [https://doi.org/10.1200/JCO.2009.26.4242 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20385984 PubMed] | ||
Line 2,002: | Line 1,928: | ||
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed] | ##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed] | ||
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed] | ##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed] | ||
− | |||
==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}== | ==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}== | ||
− | |||
Clofarabine & LoDAC: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | Clofarabine & LoDAC: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1 {{#subobject:12351c|Variant=1}}=== | ===Regimen variant #1 {{#subobject:12351c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,021: | Line 1,946: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 20 mg SC once per day on days 1 to 14, '''given 4 hours after clofarabine on days 1 to 5''' | *[[Cytarabine (Ara-C)]] 20 mg SC once per day on days 1 to 14, '''given 4 hours after clofarabine on days 1 to 5''' | ||
− | |||
'''28- to 49-day cycle for up to 2 cycles''' | '''28- to 49-day cycle for up to 2 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*CRi or better: [[#Clofarabine_.26_LoDAC_2|Clofarabine & LoDAC]] consolidation | *CRi or better: [[#Clofarabine_.26_LoDAC_2|Clofarabine & LoDAC]] consolidation | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:7d207f|Variant=1}}=== | ===Regimen variant #2 {{#subobject:7d207f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,042: | Line 1,968: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | ||
− | |||
'''10-day course''' | '''10-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients not achieving CR: Optional identical [[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]] re-induction after at least 28 days | *Patients not achieving CR: Optional identical [[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]] re-induction after at least 28 days | ||
**Patients not achieving CR after the second induction: [[#Decitabine_monotherapy_3|Decitabine]] salvage | **Patients not achieving CR after the second induction: [[#Decitabine_monotherapy_3|Decitabine]] salvage | ||
*Patients achieving CR: [[#Clofarabine_.26_LoDAC.2FDecitabine|Clofarabine & low-dose cytarabine alternating with decitabine]] consolidation | *Patients achieving CR: [[#Clofarabine_.26_LoDAC.2FDecitabine|Clofarabine & low-dose cytarabine alternating with decitabine]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218 | #'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218 | ||
#Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed] | #Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed] | ||
##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed] | ##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed] | ||
− | |||
==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}== | ==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}== | ||
− | |||
CPX-351: Liposomal Cytarabine and Daunorubicin | CPX-351: Liposomal Cytarabine and Daunorubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:0b4cdf|Variant=1}}=== | ===Regimen {{#subobject:0b4cdf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,085: | Line 2,009: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] as follows: | *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] as follows: | ||
**First induction: 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1, 3, 5 | **First induction: 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1, 3, 5 | ||
**Second induction (if needed): 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3 | **Second induction (if needed): 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3 | ||
− | |||
'''One or two courses''' | '''One or two courses''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*CR/CRi: [[#CPX-351_monotherapy_2|CPX-351]] consolidation | *CR/CRi: [[#CPX-351_monotherapy_2|CPX-351]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, FL December 4-7, 2010. --> | <!-- Presented in part in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, FL December 4-7, 2010. --> | ||
− | |||
#'''CLTR0308-204:''' Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. [http://www.bloodjournal.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687088 PubMed] NCT00788892 | #'''CLTR0308-204:''' Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. [http://www.bloodjournal.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687088 PubMed] NCT00788892 | ||
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | ||
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | ||
##'''Update:''' Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. [https://doi.org/10.1016/s2352-3026(21)00134-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34171279/ PubMed] | ##'''Update:''' Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. [https://doi.org/10.1016/s2352-3026(21)00134-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34171279/ PubMed] | ||
− | |||
==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}== | ==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen variant #1 {{#subobject:b60a91|Variant=1}}=== | ===Regimen variant #1 {{#subobject:b60a91|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,122: | Line 2,043: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''4- to 6-week cycles''' | '''4- to 6-week cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:22a24e|Variant=1}}=== | ===Regimen variant #2 {{#subobject:22a24e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,155: | Line 2,076: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*[[Hydroxyurea (Hydrea)]] (dose not specified) could be used up until cycle 1 day 15 | *[[Hydroxyurea (Hydrea)]] (dose not specified) could be used up until cycle 1 day 15 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:c6ffdd|Variant=1}}=== | ===Regimen variant #3 {{#subobject:c6ffdd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,180: | Line 2,099: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 10 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 10 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*[[Hydroxyurea (Hydrea)]] (dose not specified) allowed during and prior to cycle 1 | *[[Hydroxyurea (Hydrea)]] (dose not specified) allowed during and prior to cycle 1 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above | *OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above | ||
*OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine]] maintenance | *OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine]] maintenance | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401 | #'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401 | ||
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. --> | ||
Line 2,204: | Line 2,120: | ||
#'''JNJ AML-2002:''' Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. [https://doi.org/10.1038/s41375-020-0773-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787975/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32203138 PubMed] NCT02472145 | #'''JNJ AML-2002:''' Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. [https://doi.org/10.1038/s41375-020-0773-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787975/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32203138 PubMed] NCT02472145 | ||
#'''SEAMLESS:''' Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. [https://doi.org/10.1002/cncr.33828 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34424530/ PubMed] NCT01303796 | #'''SEAMLESS:''' Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. [https://doi.org/10.1002/cncr.33828 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34424530/ PubMed] NCT01303796 | ||
− | |||
==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}== | ==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 5 days of decitabine {{#subobject:2aab30|Variant=1}}=== | ===Regimen variant #1, 5 days of decitabine {{#subobject:2aab30|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,218: | Line 2,133: | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.'' | |
− | ''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | *[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 10 days of decitabine {{#subobject:08cde2|Variant=2}}=== | ===Regimen variant #2, 10 days of decitabine {{#subobject:08cde2|Variant=2}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,242: | Line 2,153: | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m<sup>2</sup> was allowed during cycle 1.'' | |
− | ''Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m<sup>2</sup> was allowed during cycle 1.'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 10 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 10 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Venetoclax (Venclexta)]] as follows: | *[[Venetoclax (Venclexta)]] as follows: | ||
**Cycle 1: 400 mg PO once per day | **Cycle 1: 400 mg PO once per day | ||
**Cycle 2 onwards: 400 mg PO once per day on days 1 to 21 | **Cycle 2 onwards: 400 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773] | #'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773] | ||
##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed] | ##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed] | ||
<!-- #'''Abstract:''' Maiti A, DiNardo CD, Cortes JE, Borthakur G, Pemmaraju,N, Benton CB, Kadia TM, Takahashi K, Naqvi K, Ravandi F, Alvarado Y, Short NJ, Daver NG, Sasaki K, Ohanian MN, Garcia-Manero G, Thompson PA, Kornblau SM, Masarova L, Jain N, Jabbour EJ, Andreeff M, Maduike R, Guerrero JA, Zhang Q, Cavazos A, Ma H, Rausch CR, Bivins CA, Vaughan K, Pierce SA, Ning J, Qiao W, Welch JS, Kantarjian HM, Konopleva MY. Interim Analysis of Phase II Study of Venetoclax with 10-Day Decitabine (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Blood, 132(Suppl 1), 286. [http://www.bloodjournal.org/content/132/Suppl_1/286 link to original abstract] [https://clinicaltrials.gov/ct2/show/NCT03404193 NCT03404193] --> | <!-- #'''Abstract:''' Maiti A, DiNardo CD, Cortes JE, Borthakur G, Pemmaraju,N, Benton CB, Kadia TM, Takahashi K, Naqvi K, Ravandi F, Alvarado Y, Short NJ, Daver NG, Sasaki K, Ohanian MN, Garcia-Manero G, Thompson PA, Kornblau SM, Masarova L, Jain N, Jabbour EJ, Andreeff M, Maduike R, Guerrero JA, Zhang Q, Cavazos A, Ma H, Rausch CR, Bivins CA, Vaughan K, Pierce SA, Ning J, Qiao W, Welch JS, Kantarjian HM, Konopleva MY. Interim Analysis of Phase II Study of Venetoclax with 10-Day Decitabine (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Blood, 132(Suppl 1), 286. [http://www.bloodjournal.org/content/132/Suppl_1/286 link to original abstract] [https://clinicaltrials.gov/ct2/show/NCT03404193 NCT03404193] --> | ||
#'''DEC10-VEN:''' DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. [https://doi.org/10.1016/s2352-3026(20)30210-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7549397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32896301 PubMed] NCT03404193 | #'''DEC10-VEN:''' DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. [https://doi.org/10.1016/s2352-3026(20)30210-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7549397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32896301 PubMed] NCT03404193 | ||
− | |||
==Gemtuzumab ozogamicin monotherapy {{#subobject:4e3c9a|Regimen=1}}== | ==Gemtuzumab ozogamicin monotherapy {{#subobject:4e3c9a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:e01685|Variant=1}}=== | ===Regimen {{#subobject:e01685|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,281: | Line 2,185: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV once on day 1, then 3 mg/m<sup>2</sup> IV once on day 8 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV once on day 1, then 3 mg/m<sup>2</sup> IV once on day 8 | ||
− | |||
'''8-day course''' | '''8-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin]] maintenance | *Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin]] maintenance | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. --> | <!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. --> | ||
− | |||
#'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234 | #'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234 | ||
− | |||
==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}== | ==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}== | ||
− | |||
Glasdegib & LoDAC: Glasdegib & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | Glasdegib & LoDAC: Glasdegib & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e4c7c9|Variant=1}}=== | ===Regimen {{#subobject:e4c7c9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,314: | Line 2,216: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Glasdegib (Daurismo)]] 100 mg PO once per day | *[[Glasdegib (Daurismo)]] 100 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- # '''Abstract:''' Cortes JE, Heidel FH, Heuser M, Fiedler W, Smith BD, Robak T. Montesinos Fernandez P, Ma WW, Shaik MN, Zeremski M, O'Connell A, Chan, G. A Phase 2 Randomized Study of Low Dose Ara-C with or without Glasdegib (PF-04449913) in Untreated Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. Blood 2016, 128(22), 99. [http://www.bloodjournal.org/content/128/22/99 link to original article] '''contains dosing details in manuscript''' --> | <!-- # '''Abstract:''' Cortes JE, Heidel FH, Heuser M, Fiedler W, Smith BD, Robak T. Montesinos Fernandez P, Ma WW, Shaik MN, Zeremski M, O'Connell A, Chan, G. A Phase 2 Randomized Study of Low Dose Ara-C with or without Glasdegib (PF-04449913) in Untreated Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. Blood 2016, 128(22), 99. [http://www.bloodjournal.org/content/128/22/99 link to original article] '''contains dosing details in manuscript''' --> | ||
− | |||
#'''BRIGHT AML 1003:''' Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. [https://www.nature.com/articles/s41375-018-0312-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30555165 PubMed] NCT01546038 | #'''BRIGHT AML 1003:''' Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. [https://www.nature.com/articles/s41375-018-0312-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30555165 PubMed] NCT01546038 | ||
##'''Update:''' Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. [https://doi.org/10.1007/s00277-021-04465-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8043884/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33740113/ PubMed] | ##'''Update:''' Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. [https://doi.org/10.1007/s00277-021-04465-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8043884/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33740113/ PubMed] | ||
− | |||
==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:25e1c6|Regimen=1}}== | ==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:25e1c6|Regimen=1}}== | ||
− | |||
LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
<br>LDAC: '''<u>L</u>'''ow-dose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>LDAC: '''<u>L</u>'''ow-dose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 20 mg twice per day, indefinite duration {{#subobject:a3d4fb|Variant=1}}=== | ===Regimen variant #1, 20 mg twice per day, indefinite duration {{#subobject:a3d4fb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,360: | Line 2,258: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 20 mg/m<sup>2</sup> twice per day, limited duration {{#subobject:d5c6f7|Variant=1}}=== | ===Regimen variant #2, 20 mg/m<sup>2</sup> twice per day, limited duration {{#subobject:d5c6f7|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,409: | Line 2,307: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy for UK NCRI AML16 is based on the 2016 update.'' | ''<sup>1</sup>Reported efficacy for UK NCRI AML16 is based on the 2016 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10 | ||
− | |||
'''4- to 6-week cycle for up to 4 cycles''' | '''4- to 6-week cycle for up to 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 20 mg/m<sup>2</sup> once per day, indefinite duration {{#subobject:fd61d0|Variant=1}}=== | ===Regimen variant #3, 20 mg/m<sup>2</sup> once per day, indefinite duration {{#subobject:fd61d0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,437: | Line 2,335: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.'' | ''<sup>1</sup>Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. --> | ||
− | |||
#'''DACO-016:''' Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.38.9429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689805 PubMed] NCT00260832 | #'''DACO-016:''' Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.38.9429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689805 PubMed] NCT00260832 | ||
##'''Subgroup analysis:''' Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. [https://doi.org/full/10.1002/ajh.25062 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29417613 PubMed] | ##'''Subgroup analysis:''' Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. [https://doi.org/full/10.1002/ajh.25062 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29417613 PubMed] | ||
Line 2,463: | Line 2,359: | ||
##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed] | ##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed] | ||
#'''POLO-AML-2:''' NCT01721876 | #'''POLO-AML-2:''' NCT01721876 | ||
− | |||
==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}== | ==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}== | ||
− | |||
LoDAC & Venetoclax: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & Venetoclax | LoDAC & Venetoclax: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & Venetoclax | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e84ab4|Variant=1}}=== | ===Regimen {{#subobject:e84ab4|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
Line 2,488: | Line 2,383: | ||
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup>Reported efficacy for VIALE-C is based on the 2021 update.''< | + | ''<sup>1</sup>Reported efficacy for VIALE-C is based on the 2021 update.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Venetoclax (Venclexta)]] as follows: | *[[Venetoclax (Venclexta)]] as follows: | ||
**Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28 | **Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28 | ||
**Cycle 2 onwards: 600 mg PO once per day | **Cycle 2 onwards: 600 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | ====Dose modifications==== | |
+ | *M14-387: The dose of venetoclax was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors. | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#'''M14-387:''' Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. [https://doi.org/10.1200/JCO.18.01600 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524989/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30892988 PubMed] NCT02287233 | #'''M14-387:''' Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. [https://doi.org/10.1200/JCO.18.01600 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524989/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30892988 PubMed] NCT02287233 | ||
#'''VIALE-C:''' Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. [https://doi.org/10.1182/blood.2020004856 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32219442 PubMed] NCT03069352 | #'''VIALE-C:''' Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. [https://doi.org/10.1182/blood.2020004856 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32219442 PubMed] NCT03069352 | ||
##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed] | ##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed] | ||
− | |||
==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:fb4aeb|Variant=1}}=== | ===Regimen {{#subobject:fb4aeb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,522: | Line 2,412: | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: Patient selection was based on MGMT expression by Western blot. See article for details.'' | |
− | ''Patient selection was based on MGMT expression by Western blot. See article for details.'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup>/day PO on days 1 to 7 | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup>/day PO on days 1 to 7 | ||
**Complete responders could receive: 200 mg/m<sup>2</sup>/day PO on days 1 to 5 | **Complete responders could receive: 200 mg/m<sup>2</sup>/day PO on days 1 to 5 | ||
− | |||
'''28-day cycle for up to 12 cycles''' | '''28-day cycle for up to 12 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. [https://doi.org/10.1111/bjh.13094 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25160658 PubMed] | #Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. [https://doi.org/10.1111/bjh.13094 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25160658 PubMed] | ||
− | |||
=Consolidation after upfront therapy= | =Consolidation after upfront therapy= | ||
==5+2d {{#subobject:b409f7|Regimen=1}}== | ==5+2d {{#subobject:b409f7|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:a67da7|Variant=1}}=== | ===Regimen {{#subobject:a67da7|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,549: | Line 2,435: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose | *[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | ||
− | |||
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | ||
− | |||
==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:caa3a2|Regimen=1}}== | ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:caa3a2|Regimen=1}}== | ||
− | |||
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
<br>HDAC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>HDAC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
<br>HDAraC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>AraC</u>''' (Cytarabine) | <br>HDAraC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>AraC</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 2000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:4e73ae|Variant=1}}=== | ===Regimen variant #1, 2000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:4e73ae|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,582: | Line 2,465: | ||
|} | |} | ||
''Details in the text are scant.'' | ''Details in the text are scant.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Cytarabine_.26_Mitoxantrone_.28MC.29|Cytarabine & Mitoxantrone]] consolidation | *[[#Cytarabine_.26_Mitoxantrone_.28MC.29|Cytarabine & Mitoxantrone]] consolidation | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m<sup>2</sup>) | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 2 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:2a4b32|Variant=1}}=== | ===Regimen variant #2, 2 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:2a4b32|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,609: | Line 2,493: | ||
|} | |} | ||
''Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.'' | ''Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#BHAC-MMV_88|BHAC-MMV]] | *[[#BHAC-MMV_88|BHAC-MMV]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m<sup>2</sup>) | ||
− | |||
'''28-day cycle for 2 cycles''' | '''28-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*A-VVV | *A-VVV | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1 cycle of 3000 mg/m<sup>2</sup> every 12 hours x 12 {{#subobject:a0e7d9|Variant=1}}=== | ===Regimen variant #3, 1 cycle of 3000 mg/m<sup>2</sup> every 12 hours x 12 {{#subobject:a0e7d9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,637: | Line 2,522: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#5.2B2i_88|5+2i]] | *[[#5.2B2i_88|5+2i]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>) | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 3 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:746f61|Variant=1}}=== | ===Regimen variant #4, 3 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:746f61|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,693: | Line 2,578: | ||
|} | |} | ||
''Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.'' | ''Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*CALGB 9222: [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose | *CALGB 9222: [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose | ||
*SWOG S0106: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_GO|7+3d & GO]] | *SWOG S0106: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_GO|7+3d & GO]] | ||
Line 2,701: | Line 2,586: | ||
*SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]] | *SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]] | ||
*COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | ||
− | |||
'''3 cycles of varying durations''' | '''3 cycles of varying durations''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*SWOG S0106: GO maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]] | *SWOG S0106: GO maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]] | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, 3 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:8887b8|Variant=1}}=== | ===Regimen variant #5, 3 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:8887b8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,727: | Line 2,613: | ||
|} | |} | ||
''Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.'' | ''Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B5d_88|7+5d]] or [[#7.2B3i|7+3i]] | *[[#7.2B5d_88|7+5d]] or [[#7.2B3i|7+3i]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>) | ||
− | |||
'''3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10<sup>9</sup>/L, and 100 × 10<sup>9</sup>/L''' | '''3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10<sup>9</sup>/L, and 100 × 10<sup>9</sup>/L''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #6, 4 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:0c2779|Variant=1}}=== | ===Regimen variant #6, 4 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:0c2779|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,765: | Line 2,651: | ||
|} | |} | ||
''Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.'' | ''Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*ALFA-9802: Timed sequential therapy +/- GM-CSF priming | *ALFA-9802: Timed sequential therapy +/- GM-CSF priming | ||
*COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | ||
− | |||
'''28-day cycle for up to 4 cycles''' | '''28-day cycle for up to 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*ALFA-9802: Cytarabine & Daunorubicin maintenance | *ALFA-9802: Cytarabine & Daunorubicin maintenance | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''CALGB 8525:''' Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; [[Study_Groups#CALGB|CALGB]]. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://doi.org/10.1056/NEJM199410063311402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8078551 PubMed] | #'''CALGB 8525:''' Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; [[Study_Groups#CALGB|CALGB]]. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://doi.org/10.1056/NEJM199410063311402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8078551 PubMed] | ||
#Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. [https://doi.org/10.1056/NEJM199812033392301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9834301 PubMed] | #Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. [https://doi.org/10.1056/NEJM199812033392301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9834301 PubMed] | ||
Line 2,794: | Line 2,679: | ||
#'''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://doi.org/10.1016/S1470-2045(15)00362-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26549589 PubMed] NCT00893373 | #'''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://doi.org/10.1016/S1470-2045(15)00362-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26549589 PubMed] NCT00893373 | ||
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | ||
− | |||
==Intermediate-dose Cytarabine monotherapy (IDAC) {{#subobject:f5cd74|Regimen=1}}== | ==Intermediate-dose Cytarabine monotherapy (IDAC) {{#subobject:f5cd74|Regimen=1}}== | ||
− | |||
IDAC: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | IDAC: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
<br>mIDAC: '''<u>m</u>'''odified '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>mIDAC: '''<u>m</u>'''odified '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 1000 mg/m<sup>2</sup> x 3 {{#subobject:0340ec|Variant=1}}=== | ===Regimen variant #1, 1000 mg/m<sup>2</sup> x 3 {{#subobject:0340ec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,811: | Line 2,694: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]] versus [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose | *[[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]] versus [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m<sup>2</sup>) | ||
− | |||
'''3 cycles (length not specified)''' | '''3 cycles (length not specified)''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 1000 mg/m<sup>2</sup> x 10 {{#subobject:cbba35|Variant=1}}=== | ===Regimen variant #2, 1000 mg/m<sup>2</sup> x 10 {{#subobject:cbba35|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,839: | Line 2,722: | ||
|} | |} | ||
''Note: cycle length was not specified; 28-day cycles are frequently used in this setting.'' | ''Note: cycle length was not specified; 28-day cycles are frequently used in this setting.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#BHAC-MMV_88|BHAC-MMV]] | *[[#BHAC-MMV_88|BHAC-MMV]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>) | ||
− | |||
'''28-day cycle for 2 cycles (see note)''' | '''28-day cycle for 2 cycles (see note)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*A-VVV | *A-VVV | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1000 mg/m<sup>2</sup> x 12 {{#subobject:22eda3|Variant=1}}=== | ===Regimen variant #3, 1000 mg/m<sup>2</sup> x 12 {{#subobject:22eda3|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
Line 2,863: | Line 2,747: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose versus [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose | *[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose versus [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m<sup>2</sup>) | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Transplant eligible patients: [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] | *Transplant eligible patients: [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] | ||
*Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]] | *Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377 | #'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377 | ||
#Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22287757 PubMed] | #Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22287757 PubMed] | ||
#'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637 | #'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637 | ||
− | |||
==HiDAC & G-CSF {{#subobject:e0396d|Regimen=1}}== | ==HiDAC & G-CSF {{#subobject:e0396d|Regimen=1}}== | ||
− | |||
HiDAC & G-CSF: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & '''<u>G</u>'''ranulocyte '''<u>C</u>'''olony '''<u>S</u>'''timulating '''<u>F</u>'''actor | HiDAC & G-CSF: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & '''<u>G</u>'''ranulocyte '''<u>C</u>'''olony '''<u>S</u>'''timulating '''<u>F</u>'''actor | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:d8edc4|Variant=1}}=== | ===Regimen {{#subobject:d8edc4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 2,902: | Line 2,783: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction | *[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>) | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 5 | *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 5 | ||
− | |||
'''35-day cycle for 3 cycles''' | '''35-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412 | #'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412 | ||
− | |||
==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:f7e3f6|Variant=1}}=== | ===Regimen {{#subobject:f7e3f6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,933: | Line 2,809: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin]] consolidation | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin]] consolidation | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once on day 1 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once on day 1 | ||
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | ||
− | |||
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | ||
− | |||
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}== | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:eb3f69|Variant=1}}=== | ===Regimen {{#subobject:eb3f69|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 2,961: | Line 2,834: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin]] induction | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | ||
*Growth factors per physician discretion | *Growth factors per physician discretion | ||
− | |||
'''8-day course''' | '''8-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#Azacitidine_monotherapy_2|Azacitidine]] maintenance, within 42 days of completion of consolidation | *[[#Azacitidine_monotherapy_2|Azacitidine]] maintenance, within 42 days of completion of consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). --> | ||
− | |||
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814 | ||
− | |||
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}== | ==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}== | ||
− | |||
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6ccf66|Variant=1}}=== | ===Regimen {{#subobject:6ccf66|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,006: | Line 2,873: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_.88|Amsacrine & Cytarabine]] | *[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_.88|Amsacrine & Cytarabine]] | ||
{{#lst:Autologous HSCT|6ccf66}} | {{#lst:Autologous HSCT|6ccf66}} | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
#'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed] | #'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed] | ||
− | |||
==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}== | ==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}== | ||
− | |||
BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a7e574|Variant=1}}=== | ===Regimen {{#subobject:a7e574|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,032: | Line 2,899: | ||
|} | |} | ||
{{#lst:Allogeneic HSCT|a7e574}} | {{#lst:Allogeneic HSCT|a7e574}} | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. --> | <!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. --> | ||
− | |||
#'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135 | #'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135 | ||
− | |||
==CIA {{#subobject:db5c09|Regimen=1}}== | ==CIA {{#subobject:db5c09|Regimen=1}}== | ||
− | |||
CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine) | CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:1bbed8|Variant=1}}=== | ===Regimen {{#subobject:1bbed8|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
Line 3,056: | Line 2,922: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#CIA|CIA]] induction | *[[#CIA|CIA]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
*[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity''' | '''21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed] | #Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed] | ||
− | |||
==CLARA {{#subobject:6160cf|Regimen=1}}== | ==CLARA {{#subobject:6160cf|Regimen=1}}== | ||
− | |||
CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine) | CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6ed739|Variant=1}}=== | ===Regimen {{#subobject:6ed739|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,090: | Line 2,953: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction | *[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''given first''' | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 4 hours after clofarabine, on days 2 to 5''' | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 4 hours after clofarabine, on days 2 to 5''' | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 6 | *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 6 | ||
− | |||
'''35-day cycle for 3 cycles''' | '''35-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412 | #'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412 | ||
− | |||
==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}== | ==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}== | ||
− | |||
Clofarabine & LoDAC/Decitabine: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) alternating with Decitabine | Clofarabine & LoDAC/Decitabine: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) alternating with Decitabine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol {{#subobject:0ac883|Variant=1}}=== | ===Protocol {{#subobject:0ac883|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,123: | Line 2,981: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]], which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities. | *[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]], which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities. | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, clofarabine & LoDAC portion==== | ====Chemotherapy, clofarabine & LoDAC portion==== | ||
− | |||
*[[Clofarabine (Clolar)]] as follows: | *[[Clofarabine (Clolar)]] as follows: | ||
**Cycles 2, 3, 7 to 9, 13 to 15: 20 mg/m<sup>2</sup> IV once per day on days 1 to 3 | **Cycles 2, 3, 7 to 9, 13 to 15: 20 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Cytarabine (Ara-C)]] as follows: | *[[Cytarabine (Ara-C)]] as follows: | ||
**Cycles 2, 3, 7 to 9, 13 to 15: 20 mg SC twice per day on days 1 to 7 | **Cycles 2, 3, 7 to 9, 13 to 15: 20 mg SC twice per day on days 1 to 7 | ||
− | |||
'''4- to 7-week cycles, depending on count recovery''' | '''4- to 7-week cycles, depending on count recovery''' | ||
− | |||
====Chemotherapy, decitabine portion==== | ====Chemotherapy, decitabine portion==== | ||
− | |||
*[[Decitabine (Dacogen)]] as follows: | *[[Decitabine (Dacogen)]] as follows: | ||
**Cycles 4 to 6, 10 to 12, 16 to 18: 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | **Cycles 4 to 6, 10 to 12, 16 to 18: 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
'''4- to 7-week cycles, depending on count recovery''' | '''4- to 7-week cycles, depending on count recovery''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed] | #Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed] | ||
##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed] | ##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed] | ||
− | |||
==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}== | ==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}== | ||
− | |||
CPX-351: Liposomal Cytarabine and Daunorubicin | CPX-351: Liposomal Cytarabine and Daunorubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:896083|Variant=1}}=== | ===Regimen {{#subobject:896083|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,162: | Line 3,014: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#CPX-351_monotherapy|CPX-351]] induction | *[[#CPX-351_monotherapy|CPX-351]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] 65 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3 | *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] 65 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3 | ||
− | |||
'''5- to 8-week cycle for 2 cycles''' | '''5- to 8-week cycle for 2 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] --> | ||
− | |||
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084 | ||
− | |||
==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}== | ==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:c39b55|Variant=1}}=== | ===Regimen variant #1 {{#subobject:c39b55|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,191: | Line 3,040: | ||
|} | |} | ||
''Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10<sup>9</sup> at day 45 from initiation of chemotherapy were assigned to this regimen.'' | ''Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10<sup>9</sup> at day 45 from initiation of chemotherapy were assigned to this regimen.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose or [[#7.2B3d_.26_GO|7+3d & GO]] induction | *[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose or [[#7.2B3d_.26_GO|7+3d & GO]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] as follows: | *[[Daunorubicin (Cerubidine)]] as follows: | ||
**Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1 | **Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1 | ||
**Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | **Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | |||
'''2 cycles (length not specified)''' | '''2 cycles (length not specified)''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:59874e|Variant=1}}=== | ===Regimen variant #2 {{#subobject:59874e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,219: | Line 3,068: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B4d_88|4d + 7]] induction | *[[#7.2B4d_88|4d + 7]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''1-month cycle for up to 6 cycles''' | '''1-month cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025 | #'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025 | ||
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | ||
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ||
− | |||
==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}== | ==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:c56261|Variant=1}}=== | ===Regimen {{#subobject:c56261|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,249: | Line 3,095: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.26_GO|7+3d & GO]] induction | *[[#7.2B3d_.26_GO|7+3d & GO]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] as follows: | *[[Daunorubicin (Cerubidine)]] as follows: | ||
**Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1 | **Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1 | ||
**Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | **Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | |||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once on day 1 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once on day 1 | ||
− | |||
'''2 cycles (length not specified)''' | '''2 cycles (length not specified)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498 | ||
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed] | ||
− | |||
==CYVE {{#subobject:f8d436|Regimen=1}}== | ==CYVE {{#subobject:f8d436|Regimen=1}}== | ||
− | |||
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide) | CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:79438d|Variant=1}}=== | ===Regimen {{#subobject:79438d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,286: | Line 3,127: | ||
|} | |} | ||
''Note: this consolidation regimen was for patients with high-risk cytogenetics.'' | ''Note: this consolidation regimen was for patients with high-risk cytogenetics.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | *[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]] | ||
− | <div class="toccolours" style=" | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6 | ||
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''4 courses''' | '''4 courses''' | ||
</div> | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Transplant eligible patients with available donors usually proceeded to [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] after 2 courses (details not specified) | *Transplant eligible patients with available donors usually proceeded to [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] after 2 courses (details not specified) | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846 | ||
==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}== | ==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:099908|Variant=1}}=== | ===Regimen {{#subobject:099908|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,322: | Line 3,161: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B4i_88|4i + 7]] induction | *[[#7.2B4i_88|4i + 7]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 9 mg/m<sup>2</sup> IV once on day 1 | *[[Idarubicin (Idamycin)]] 9 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''1-month cycle for up to 6 cycles''' | '''1-month cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025 | #'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025 | ||
− | |||
==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}== | ==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:97a478|Variant=1}}=== | ===Regimen {{#subobject:97a478|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,351: | Line 3,187: | ||
|} | |} | ||
''Regimen details are from the phase 2 part of the published phase 1/2 trial.'' | ''Regimen details are from the phase 2 part of the published phase 1/2 trial.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib]] induction | *[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 2250 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 2250 mg/m<sup>2</sup>) | ||
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2 | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day for up to 28 days | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day for up to 28 days | ||
− | |||
'''4- to 6-week cycle for up to 5 cycles''' | '''4- to 6-week cycle for up to 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#Sorafenib_monotherapy|Sorafenib]] maintenance | *[[#Sorafenib_monotherapy|Sorafenib]] maintenance | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | ||
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ||
− | |||
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}== | ==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}== | ||
− | |||
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6ca28d|Variant=1}}=== | ===Regimen {{#subobject:6ca28d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,409: | Line 3,241: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then [[Stub#Amsacrine_.26_IDAC|Amsacrine & IDAC]] | *Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then [[Stub#Amsacrine_.26_IDAC|Amsacrine & IDAC]] | ||
{{#lst:Allogeneic HSCT|6ca28d}} | {{#lst:Allogeneic HSCT|6ca28d}} | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https://doi.org/10.1056/NEJM198005083021901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6245359 PubMed] | #Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https://doi.org/10.1056/NEJM198005083021901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6245359 PubMed] | ||
#Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https://doi.org/10.1056/NEJM199501263320403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7808487 PubMed] | #Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https://doi.org/10.1056/NEJM199501263320403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7808487 PubMed] | ||
#'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878 | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878 | ||
#'''Retrospective:''' Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. [http://www.bloodjournal.org/content/122/24/3863.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854108/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24065243 PubMed] | #'''Retrospective:''' Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. [http://www.bloodjournal.org/content/122/24/3863.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854108/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24065243 PubMed] | ||
− | |||
==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}== | ==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}== | ||
− | |||
ME: '''<u>M</u>'''itoxantrone & '''<u>E</u>'''toposide | ME: '''<u>M</u>'''itoxantrone & '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 3 days {{#subobject:78ghc3|Variant=1}}=== | ===Regimen variant #1, 3 days {{#subobject:78ghc3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,444: | Line 3,275: | ||
|} | |} | ||
''Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.'' | ''Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[#7.2B3d_.28intermediate-dose.29|7+3d]] induction | *[[#7.2B3d_.28intermediate-dose.29|7+3d]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''One course''' | '''One course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 5 days {{#subobject:780933|Variant=1}}=== | ===Regimen variant #2, 5 days {{#subobject:780933|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,469: | Line 3,301: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]] | *[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
'''One course''' | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed] | #'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed] | ||
#'''AMLSG31-19:''' NCT04628026 | #'''AMLSG31-19:''' NCT04628026 | ||
− | |||
==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}== | ==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:be3609|Variant=1}}=== | ===Regimen variant #1 {{#subobject:be3609|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,505: | Line 3,335: | ||
{{#lst:Allogeneic HSCT|be3609}} | {{#lst:Allogeneic HSCT|be3609}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}=== | ===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,522: | Line 3,352: | ||
{{#lst:Allogeneic HSCT|7fa6ce}} | {{#lst:Allogeneic HSCT|7fa6ce}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed] | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed] | ||
#'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878 | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878 | ||
− | |||
==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}== | ==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:dd1486|Variant=1}}=== | ===Regimen {{#subobject:dd1486|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,547: | Line 3,374: | ||
{{#lst:Allogeneic HSCT|dd1486}} | {{#lst:Allogeneic HSCT|dd1486}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. --> | <!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. --> | ||
− | |||
#'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135 | #'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135 | ||
− | |||
==HAM {{#subobject:1da5a5|Regimen=1}}== | ==HAM {{#subobject:1da5a5|Regimen=1}}== | ||
− | |||
HAM: '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone | HAM: '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:eb86c6|Variant=1}}=== | ===Regimen {{#subobject:eb86c6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,575: | Line 3,398: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*Wierzbowska et al. 2007: [[#CLAG-M|CLAG-M]] | *Wierzbowska et al. 2007: [[#CLAG-M|CLAG-M]] | ||
*PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus [[#DAF_99|DAF]] | *PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus [[#DAF_99|DAF]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 3 to 5 | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 3 to 5 | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org] | #Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org] | ||
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed] | #'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed] | ||
− | |||
==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}== | ==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}== | ||
− | |||
IC & Norethandrolone: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, Norethandrolone | IC & Norethandrolone: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, Norethandrolone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol {{#subobject:0849b9|Variant=1}}=== | ===Protocol {{#subobject:0849b9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,611: | Line 3,432: | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#ICL|7+3i & Lomustine]] | *[[#ICL|7+3i & Lomustine]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, reinduction==== | ====Chemotherapy, reinduction==== | ||
− | |||
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once on day 1 | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m<sup>2</sup>) | ||
− | |||
====Endocrince therapy, reinduction==== | ====Endocrince therapy, reinduction==== | ||
− | |||
*[[Norethandrolone (Nilevar)]] by the following weight-based criteria: | *[[Norethandrolone (Nilevar)]] by the following weight-based criteria: | ||
**If less than 60 kg: 10 mg PO once per day | **If less than 60 kg: 10 mg PO once per day | ||
**If greater than 60 kg: 20 mg PO once per day | **If greater than 60 kg: 20 mg PO once per day | ||
− | |||
'''3-month cycle for 6 cycles, alternating with maintenance''' | '''3-month cycle for 6 cycles, alternating with maintenance''' | ||
====Chemotherapy, maintenance==== | ====Chemotherapy, maintenance==== | ||
− | |||
*[[Methotrexate (MTX)]] by the following weight-based criteria: | *[[Methotrexate (MTX)]] by the following weight-based criteria: | ||
**If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11 | **If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11 | ||
Line 3,635: | Line 3,452: | ||
**If less than 60 kg: 100 mg PO once per day on days 15 to 30 | **If less than 60 kg: 100 mg PO once per day on days 15 to 30 | ||
**If greater than 60 kg: 150 mg PO once per day on days 15 to 30 | **If greater than 60 kg: 150 mg PO once per day on days 15 to 30 | ||
− | |||
====Endocrine therapy, maintenance==== | ====Endocrine therapy, maintenance==== | ||
− | |||
*[[Norethandrolone (Nilevar)]] by the following weight-based criteria: | *[[Norethandrolone (Nilevar)]] by the following weight-based criteria: | ||
**If less than 60 kg: 10 mg PO once per day | **If less than 60 kg: 10 mg PO once per day | ||
**If greater than 60 kg: 20 mg PO once per day | **If greater than 60 kg: 20 mg PO once per day | ||
− | |||
'''3-month cycle for 6 cycles, alternating with re-induction courses''' | '''3-month cycle for 6 cycles, alternating with re-induction courses''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''GOELAMS LAM-SA2002:''' Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. [https://doi.org/10.1200/JCO.2016.67.6213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129526 PubMed] NCT00700544 | #'''GOELAMS LAM-SA2002:''' Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. [https://doi.org/10.1200/JCO.2016.67.6213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129526 PubMed] NCT00700544 | ||
− | |||
==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}== | ==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}== | ||
− | |||
TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:174a8e|Variant=1}}=== | ===Regimen {{#subobject:174a8e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,664: | Line 3,476: | ||
{{#lst:Allogeneic HSCT|174a8e}} | {{#lst:Allogeneic HSCT|174a8e}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed] | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed] | ||
− | |||
=Maintenance after first-line therapy= | =Maintenance after first-line therapy= | ||
''Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.'' | ''Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.'' | ||
==Azacitidine monotherapy {{#subobject:887fd6|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:887fd6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 12 cycles {{#subobject:482f12|Variant=1}}=== | ===Regimen variant #1, 12 cycles {{#subobject:482f12|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,692: | Line 3,501: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*At least 2 cycles of [[Regimen_classes#Intensive_chemotherapy|intensive chemotherapy]] | *At least 2 cycles of [[Regimen_classes#Intensive_chemotherapy|intensive chemotherapy]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 50 mg/m<sup>2</sup> SC once per day on days 1 to 5 | *[[Azacitidine (Vidaza)]] 50 mg/m<sup>2</sup> SC once per day on days 1 to 5 | ||
− | |||
'''28-day cycle for up to 12 cycles''' | '''28-day cycle for up to 12 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, indefinite {{#subobject:482f11|Variant=1}}=== | ===Regimen variant #2, indefinite {{#subobject:482f11|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,714: | Line 3,523: | ||
|} | |} | ||
''Intended to be used for transformed MDS patients in remission after AML induction therapy.'' | ''Intended to be used for transformed MDS patients in remission after AML induction therapy.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B2d_88|7+2d]] | *[[#7.2B2d_88|7+2d]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5 | *[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. [https://doi.org/10.1111/j.1365-2141.2010.08235.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20497178 PubMed] | #Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. [https://doi.org/10.1111/j.1365-2141.2010.08235.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20497178 PubMed] | ||
#'''HOVON97:''' Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. [https://doi.org/10.1182/blood-2018-10-879866 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30630862 PubMed] NTR1810 | #'''HOVON97:''' Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. [https://doi.org/10.1182/blood-2018-10-879866 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30630862 PubMed] NTR1810 | ||
− | |||
==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}== | ==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:4726aa|Variant=1}}=== | ===Regimen {{#subobject:4726aa|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,744: | Line 3,549: | ||
|} | |} | ||
''Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.'' | ''Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Decitabine_monotherapy|Decitabine]] induction | *[[#Decitabine_monotherapy|Decitabine]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
**Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC less than 500/uL) persisting greater than or equal to 14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle. | **Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC less than 500/uL) persisting greater than or equal to 14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle. | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401 | #'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401 | ||
− | |||
==Azacitidine oral monotherapy {{#subobject:da9efa|Regimen=1}}== | ==Azacitidine oral monotherapy {{#subobject:da9efa|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:90f116|Variant=1}}=== | ===Regimen {{#subobject:90f116|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,777: | Line 3,579: | ||
|} | |} | ||
''<sup>1</sup>The proportional hazards assumption was violated, so hazard ratios are not reported.'' | ''<sup>1</sup>The proportional hazards assumption was violated, so hazard ratios are not reported.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Regimen_classes#Chemotherapy|Induction chemotherapy]] | *[[Regimen_classes#Chemotherapy|Induction chemotherapy]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine oral (Onureg)]] 300 mg PO once per day on days 1 to 14 | *[[Azacitidine oral (Onureg)]] 300 mg PO once per day on days 1 to 14 | ||
− | |||
'''28-day cycle''' | '''28-day cycle''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''QUAZAR AML-001:''' Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. [https://doi.org/10.1056/nejmoa2004444 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33369355 PubMed] NCT01757535 | #'''QUAZAR AML-001:''' Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. [https://doi.org/10.1056/nejmoa2004444 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33369355 PubMed] NCT01757535 | ||
− | |||
==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}== | ==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:b7c813|Variant=1}}=== | ===Regimen {{#subobject:b7c813|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
Line 3,804: | Line 3,603: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin]] induction, with clinical benefit | *[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin]] induction, with clinical benefit | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 2 mg/m<sup>2</sup> IV once on day 1 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 2 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''1-month cycle for up to 8 cycles''' | '''1-month cycle for up to 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. --> | <!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. --> | ||
− | |||
#'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234 | #'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234 | ||
− | |||
==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:4c65c8|Regimen=1}}== | ==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:4c65c8|Regimen=1}}== | ||
− | |||
LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | ||
<br>LDAC: '''<u>L</u>'''ow '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | <br>LDAC: '''<u>L</u>'''ow '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:2f5aa0|Variant=1}}=== | ===Regimen {{#subobject:2f5aa0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,839: | Line 3,634: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_88|HiDAC]], then [[#Amsacrine_monotherapy_88|amsacrine]] induction | *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_88|HiDAC]], then [[#Amsacrine_monotherapy_88|amsacrine]] induction | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 10 mg/m<sup>2</sup> SC twice per day on days 1 to 21 | *[[Cytarabine (Ara-C)]] 10 mg/m<sup>2</sup> SC twice per day on days 1 to 21 | ||
− | |||
'''8-week cycles''' | '''8-week cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''ECOG E5483:''' Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. [https://www.nature.com/articles/2401850 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10942228 PubMed] | #'''ECOG E5483:''' Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. [https://www.nature.com/articles/2401850 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10942228 PubMed] | ||
− | |||
==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== | ==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:b50325|Variant=1}}=== | ===Regimen {{#subobject:b50325|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,867: | Line 3,658: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib]] consolidation | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib]] consolidation | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | ||
− | |||
'''Up to one year course, including consolidation''' | '''Up to one year course, including consolidation''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971 | ||
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed] | ||
− | |||
=Relapsed or refractory, salvage therapy= | =Relapsed or refractory, salvage therapy= | ||
''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.'' | ''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.'' | ||
==5+2d {{#subobject:df9bab|Regimen=1}}== | ==5+2d {{#subobject:df9bab|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:c9d569|Variant=1}}=== | ===Regimen {{#subobject:c9d569|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,898: | Line 3,686: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose | *[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>) | ||
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972 | #'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972 | ||
− | |||
==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}== | ==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}== | ||
− | |||
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:a99e51|Variant=1}}=== | ===Regimen {{#subobject:a99e51|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 3,932: | Line 3,716: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] as follows: | *[[Cytarabine (Ara-C)]] as follows: | ||
**Course 1: 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m<sup>2</sup>) | **Course 1: 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m<sup>2</sup>) | ||
Line 3,940: | Line 3,723: | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | |||
'''2 courses (length not specified)''' | '''2 courses (length not specified)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''MRC AML-HR:''' Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. [http://www.bloodjournal.org/content/107/12/4614.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16484584 PubMed] NCT00005863 | #'''MRC AML-HR:''' Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. [http://www.bloodjournal.org/content/107/12/4614.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16484584 PubMed] NCT00005863 | ||
− | |||
==CLAG {{#subobject:702383|Regimen=1}}== | ==CLAG {{#subobject:702383|Regimen=1}}== | ||
− | |||
CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF | CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:12d1bb|Variant=1}}=== | ===Regimen {{#subobject:12d1bb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,962: | Line 3,741: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine''' | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine) | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine) | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. [https://doi.org/10.3109/10428190009053545 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10975390 PubMed] | #Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. [https://doi.org/10.3109/10428190009053545 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10975390 PubMed] | ||
#'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed] | #'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed] | ||
− | |||
==CLAG-M {{#subobject:51b417|Regimen=1}}== | ==CLAG-M {{#subobject:51b417|Regimen=1}}== | ||
− | |||
CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone | CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e0b308|Variant=1}}=== | ===Regimen {{#subobject:e0b308|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 3,990: | Line 3,765: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine''' | ||
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] by the following criteria: | *[[Filgrastim (Neupogen)]] by the following criteria: | ||
**WBC count less than or equal to 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 0 to 5, '''started 24 hours prior to chemotherapy''' | **WBC count less than or equal to 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 0 to 5, '''started 24 hours prior to chemotherapy''' | ||
**WBC count greater than 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 1 to 5, '''started simultaneously to cladribine''' | **WBC count greater than 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 1 to 5, '''started simultaneously to cladribine''' | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with PR were recommended to undergo a second course of [[#CLAG-M|CLAG-M]]. | *Patients with PR were recommended to undergo a second course of [[#CLAG-M|CLAG-M]]. | ||
**Primary refractory patients achieving CR after 2nd CLAG-M: [[#HAM|HAM]] consolidation | **Primary refractory patients achieving CR after 2nd CLAG-M: [[#HAM|HAM]] consolidation | ||
*Others could receive another course of CLAG-M or [[#HAM|HAM]] consolidation per investigator discretion | *Others could receive another course of CLAG-M or [[#HAM|HAM]] consolidation per investigator discretion | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org] | #Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org] | ||
#'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed] | #'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed] | ||
− | |||
==CLARA {{#subobject:48978a|Regimen=1}}== | ==CLARA {{#subobject:48978a|Regimen=1}}== | ||
− | |||
CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine) | CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine) | ||
<br>GCLAC: '''<u>G</u>'''-CSF, '''<u>C</u>'''lofarabine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>GCLAC: '''<u>G</u>'''-CSF, '''<u>C</u>'''lofarabine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:b8a3a2|Variant=1}}=== | ===Regimen {{#subobject:b8a3a2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,029: | Line 3,800: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | *[[Clofarabine (Clolar)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after start of clofarabine infusion''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after start of clofarabine infusion''' | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Patients with greater than 5% blasts at day 21: [[#CLARA_2|CLARA]] re-induction x 1 | *Patients with greater than 5% blasts at day 21: [[#CLARA_2|CLARA]] re-induction x 1 | ||
*Patients achieving CR: Optional [[#CLARA_3|CLARA]] consolidation for up to 2 cycles | *Patients achieving CR: Optional [[#CLARA_3|CLARA]] consolidation for up to 2 cycles | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''UW 6562:''' Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. [https://doi.org/10.1111/j.1365-2141.2011.08831.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21848522 PubMed] NCT00602225 | #'''UW 6562:''' Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. [https://doi.org/10.1111/j.1365-2141.2011.08831.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21848522 PubMed] NCT00602225 | ||
− | |||
==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}== | ==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 20/20 variant 1 {{#subobject:d4a73c|Variant=1}}=== | ===Regimen variant #1, 20/20 variant 1 {{#subobject:d4a73c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,061: | Line 3,828: | ||
|- | |- | ||
|} | |} | ||
− | ''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.'' | + | ''Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10 | *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10 | ||
− | |||
'''Cycle duration not explicitly defined; presumably 28 days''' | '''Cycle duration not explicitly defined; presumably 28 days''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 20/20 variant 2 {{#subobject:dhg73c|Variant=1}}=== | ===Regimen variant #2, 20/20 variant 2 {{#subobject:dhg73c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,080: | Line 3,847: | ||
|- | |- | ||
|} | |} | ||
− | ''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.'' | + | ''Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 14 | *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 14 | ||
− | |||
'''Cycle duration not explicitly defined; presumably 28 days''' | '''Cycle duration not explicitly defined; presumably 28 days''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 30/1000 {{#subobject:f6ada8|Variant=1}}=== | ===Regimen variant #3, 30/1000 {{#subobject:f6ada8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,099: | Line 3,866: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
'''At least one cycle''' | '''At least one cycle''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*Chemo-responsive patients: [[#Clofarabine_.26_Melphalan.2C_then_allo_HSCT|Clofarabine & Melphalan, then allo HSCT]] | *Chemo-responsive patients: [[#Clofarabine_.26_Melphalan.2C_then_allo_HSCT|Clofarabine & Melphalan, then allo HSCT]] | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 40/1000 {{#subobject:d95457|Variant=1}}=== | ===Regimen variant #4, 40/1000 {{#subobject:d95457|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,137: | Line 3,905: | ||
|} | |} | ||
''Note: length of cycles was not specified; 28-day cycle is typical for this regimen.'' | ''Note: length of cycles was not specified; 28-day cycle is typical for this regimen.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | *[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | ||
**Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6 | **Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 3 to 4 hours after completion of clofarabine infusion''' | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 3 to 4 hours after completion of clofarabine infusion''' | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*Best described in Agura et al. 2011 | *Best described in Agura et al. 2011 | ||
*[[Dexamethasone (Decadron)]] 10 mg IV once per day | *[[Dexamethasone (Decadron)]] 10 mg IV once per day | ||
Line 4,157: | Line 3,923: | ||
*Parenteral nutrition allowed | *Parenteral nutrition allowed | ||
*No routine use of growth factors | *No routine use of growth factors | ||
− | |||
'''28-day cycle for 1 to 4 cycles''' | '''28-day cycle for 1 to 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*See individual papers for details | *See individual papers for details | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. [http://www.bloodjournal.org/content/105/3/940.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15486072 PubMed] | #Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. [http://www.bloodjournal.org/content/105/3/940.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15486072 PubMed] | ||
#'''Baylor 004-145:''' Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. [http://theoncologist.alphamedpress.org/content/16/2/197.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21273514 PubMed] NCT00334074 | #'''Baylor 004-145:''' Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. [http://theoncologist.alphamedpress.org/content/16/2/197.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21273514 PubMed] NCT00334074 | ||
Line 4,171: | Line 3,936: | ||
#'''FHCRC 2302.00:''' Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25854284 PubMed] | #'''FHCRC 2302.00:''' Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25854284 PubMed] | ||
#'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed] | #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed] | ||
− | |||
==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}== | ==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:7683cc|Variant=1}}=== | ===Regimen {{#subobject:7683cc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
Line 4,187: | Line 3,951: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | ||
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 5 | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 5 | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. [https://doi.org/10.1200/jco.1988.6.2.213 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3422260 PubMed] | #Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. [https://doi.org/10.1200/jco.1988.6.2.213 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3422260 PubMed] | ||
− | |||
==FLAG {{#subobject:551761|Regimen=1}}== | ==FLAG {{#subobject:551761|Regimen=1}}== | ||
− | |||
FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF | FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:9501d2|Variant=1}}=== | ===Regimen {{#subobject:9501d2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,210: | Line 3,972: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first''' | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after the start of fludarabine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after the start of fludarabine''' | ||
− | |||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
− | |||
*G-CSF with one of the following: | *G-CSF with one of the following: | ||
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery | **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery | ||
**[[Lenograstim (Granocyte)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery | **[[Lenograstim (Granocyte)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. [https://doi.org/10.1002/(sici)1096-8652(199806)58:2%3C105::aid-ajh3%3E3.0.co;2-w link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9625576 PubMed] | #Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. [https://doi.org/10.1002/(sici)1096-8652(199806)58:2%3C105::aid-ajh3%3E3.0.co;2-w link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9625576 PubMed] | ||
− | |||
==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}== | ==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}== | ||
− | |||
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Filgrastim), '''<u>Ida</u>'''rubicin | FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Filgrastim), '''<u>Ida</u>'''rubicin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5fa1bb|Variant=1}}=== | ===Regimen {{#subobject:5fa1bb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,246: | Line 4,003: | ||
|} | |} | ||
''Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.'' | ''Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first''' | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after fludarabine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after fludarabine''' | ||
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
#Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. [https://doi.org/10.1046/j.1365-2141.1997.4763281.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432047 PubMed] | #Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. [https://doi.org/10.1046/j.1365-2141.1997.4763281.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432047 PubMed] | ||
#Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. [https://doi.org/10.1007/s00277-003-0624-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12707726 PubMed] | #Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. [https://doi.org/10.1007/s00277-003-0624-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12707726 PubMed] | ||
− | |||
==F-SHAI {{#subobject:9e1c5f|Regimen=1}}== | ==F-SHAI {{#subobject:9e1c5f|Regimen=1}}== | ||
− | |||
F-SHAI: '''<u>F</u>'''ludarabine, '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>I</u>'''darubicin | F-SHAI: '''<u>F</u>'''ludarabine, '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>I</u>'''darubicin | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:b50224|Variant=1}}=== | ===Regimen {{#subobject:b50224|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,282: | Line 4,034: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 15 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9, '''given 4 hours prior to each cytarabine dose''' | *[[Fludarabine (Fludara)]] 15 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9, '''given 4 hours prior to each cytarabine dose''' | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9 | ||
**Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse | **Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse | ||
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11 | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | |||
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL | ||
**Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts | **Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts | ||
− | |||
'''11-day course''' | '''11-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://doi.org/10.1038/leu.2013.297 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24150216 PubMed] | #Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://doi.org/10.1038/leu.2013.297 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24150216 PubMed] | ||
− | |||
==Gemtuzumab ozogamicin monotherapy {{#subobject:4e1hba|Regimen=1}}== | ==Gemtuzumab ozogamicin monotherapy {{#subobject:4e1hba|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, fractionated dosing {{#subobject:jgaci5|Variant=1}}=== | ===Regimen variant #1, fractionated dosing {{#subobject:jgaci5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,313: | Line 4,060: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 4, 7 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 4, 7 | ||
− | |||
'''One course''' | '''One course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:e0aci5|Variant=1}}=== | ===Regimen variant #2 {{#subobject:e0aci5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,331: | Line 4,078: | ||
|} | |} | ||
''Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.'' | ''Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Gemtuzumab ozogamicin (Mylotarg)]] 9 mg/m<sup>2</sup> IV once on day 1 | *[[Gemtuzumab ozogamicin (Mylotarg)]] 9 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''14-day cycle for 2 cycles''' | '''14-day cycle for 2 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
# Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [https://doi.org/10.1200/jco.2001.19.13.3244 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11432892 PubMed] | # Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [https://doi.org/10.1200/jco.2001.19.13.3244 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11432892 PubMed] | ||
Line 4,342: | Line 4,088: | ||
## '''Update:''' Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. [https://doi.org/full/10.1002/cncr.21326 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16116598 PubMed] | ## '''Update:''' Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. [https://doi.org/full/10.1002/cncr.21326 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16116598 PubMed] | ||
#'''MyloFrance-1:''' Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. [https://doi.org/10.1038/sj.leu.2404434 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17051246/ PubMed] | #'''MyloFrance-1:''' Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. [https://doi.org/10.1038/sj.leu.2404434 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17051246/ PubMed] | ||
− | |||
==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:1dddf5|Regimen=1}}== | ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:1dddf5|Regimen=1}}== | ||
− | |||
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, CI {{#subobject:e8a7af|Variant=1}}=== | ===Regimen variant #1, CI {{#subobject:e8a7af|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,362: | Line 4,107: | ||
|} | |} | ||
''Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.'' | ''Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m<sup>2</sup>) | ||
− | |||
'''3-day course''' | '''3-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, intermittent {{#subobject:ab6f08|Variant=1}}=== | ===Regimen variant #2, intermittent {{#subobject:ab6f08|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,383: | Line 4,128: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>) | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#'''SWOG-8326:''' Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. [https://doi.org/10.1016/s0145-2126(99)00087-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10475617 PubMed] | #'''SWOG-8326:''' Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. [https://doi.org/10.1016/s0145-2126(99)00087-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10475617 PubMed] | ||
#'''VION-CLI-037:''' Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. [http://www.bloodjournal.org/content/114/19/4027.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19710500 PubMed] NCT00112554 | #'''VION-CLI-037:''' Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. [http://www.bloodjournal.org/content/114/19/4027.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19710500 PubMed] NCT00112554 | ||
− | |||
==MAC {{#subobject:fba448|Regimen=1}}== | ==MAC {{#subobject:fba448|Regimen=1}}== | ||
− | |||
MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
<br>MIDAC: '''<u>M</u>'''itoxantrone & '''<u>I</u>'''ntermediate-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | <br>MIDAC: '''<u>M</u>'''itoxantrone & '''<u>I</u>'''ntermediate-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 6000/25 {{#subobject:5bf868|Variant=1}}=== | ===Regimen variant #1, 6000/25 {{#subobject:5bf868|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,408: | Line 4,151: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 5 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | *[[Mitoxantrone (Novantrone)]] 5 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m<sup>2</sup>) | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 10,000/48 {{#subobject:4a2f44|Variant=1}}=== | ===Regimen variant #2, 10,000/48 {{#subobject:4a2f44|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,430: | Line 4,173: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 2 to 5 | *[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 2 to 5 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>) | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. [http://www.bloodjournal.org/content/88/4/1198.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8695837 PubMed] | #Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. [http://www.bloodjournal.org/content/88/4/1198.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8695837 PubMed] | ||
#Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. [https://doi.org/10.1002/(sici)1097-0142(20000501)88:9%3C2037::aid-cncr8%3E3.0.co;2-k link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10813714 PubMed] | #Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. [https://doi.org/10.1002/(sici)1097-0142(20000501)88:9%3C2037::aid-cncr8%3E3.0.co;2-k link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10813714 PubMed] | ||
− | |||
==MEC {{#subobject:48e49b|Regimen=1}}== | ==MEC {{#subobject:48e49b|Regimen=1}}== | ||
− | |||
MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine | MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 6/80/1000 {{#subobject:ac3985|Variant=1}}=== | ===Regimen variant #1, 6/80/1000 {{#subobject:ac3985|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,456: | Line 4,196: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1 to 6 | *[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1 to 6 | ||
*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 6 | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 6 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 6 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 6 | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 8/80/1000 {{#subobject:9ad362|Variant=1}}=== | ===Regimen variant #2, 8/80/1000 {{#subobject:9ad362|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,479: | Line 4,219: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 6 | *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 6 | ||
*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 6 | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 6 | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6 | ||
− | |||
'''6-day course''' | '''6-day course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 8/100/1000 {{#subobject:bd7f87|Variant=1}}=== | ===Regimen variant #3, 8/100/1000 {{#subobject:bd7f87|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,509: | Line 4,249: | ||
|} | |} | ||
''Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.'' | ''Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV push once per day on days 1 to 5, '''given third''' | *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV push once per day on days 1 to 5, '''given third''' | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first''' | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | ||
− | |||
'''28-day cycle for 1 to 2 cycles''' | '''28-day cycle for 1 to 2 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. [https://doi.org/10.1200/jco.1991.9.7.1210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2045861 PubMed] | #Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. [https://doi.org/10.1200/jco.1991.9.7.1210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2045861 PubMed] | ||
#'''ECOG E2995:''' Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004 Jul 1;22(13):2747. [https://doi.org/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020609 PubMed] | #'''ECOG E2995:''' Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004 Jul 1;22(13):2747. [https://doi.org/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020609 PubMed] | ||
Line 4,523: | Line 4,262: | ||
#'''CLTR0308-205:''' Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015 Jan 15;121(2):234-42. Epub 2014 Sep 15. [https://doi.org/10.1002/cncr.28974 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25223583 PubMed] NCT00822094 | #'''CLTR0308-205:''' Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015 Jan 15;121(2):234-42. Epub 2014 Sep 15. [https://doi.org/10.1002/cncr.28974 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25223583 PubMed] NCT00822094 | ||
#'''D18-11141:''' NCT03926624 | #'''D18-11141:''' NCT03926624 | ||
− | |||
=Consolidation after salvage therapy= | =Consolidation after salvage therapy= | ||
==BuCy, then allo HSCT {{#subobject:83e07a|Regimen=1}}== | ==BuCy, then allo HSCT {{#subobject:83e07a|Regimen=1}}== | ||
− | |||
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 12.8/120 {{#subobject:eeaff3|Variant=1}}=== | ===Regimen variant #1, 12.8/120 {{#subobject:eeaff3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,551: | Line 4,289: | ||
{{#lst:Allogeneic HSCT|eeaff3}} | {{#lst:Allogeneic HSCT|eeaff3}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 16/200 {{#subobject:334af6|Variant=1}}=== | ===Regimen variant #2, 16/200 {{#subobject:334af6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,568: | Line 4,306: | ||
{{#lst:Allogeneic HSCT|334af6}} | {{#lst:Allogeneic HSCT|334af6}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. [https://doi.org/10.1056/NEJM198312013092202 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6355849 PubMed] | #Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. [https://doi.org/10.1056/NEJM198312013092202 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6355849 PubMed] | ||
#'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957 | #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957 | ||
#'''BMT CTN 0901:''' Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. [https://doi.org/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28380315 PubMed] NCT01339910 | #'''BMT CTN 0901:''' Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. [https://doi.org/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28380315 PubMed] NCT01339910 | ||
− | |||
==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}== | ==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}== | ||
− | |||
BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | ||
<br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan | <br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1 {{#subobject:d415a|Variant=1}}=== | ===Regimen variant #1 {{#subobject:d415a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,599: | Line 4,334: | ||
{{#lst:Allogeneic HSCT|d415a}} | {{#lst:Allogeneic HSCT|d415a}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:d415b|Variant=1}}=== | ===Regimen variant #2 {{#subobject:d415b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,619: | Line 4,354: | ||
{{#lst:Allogeneic HSCT|d415b}} | {{#lst:Allogeneic HSCT|d415b}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:d415c|Variant=1}}=== | ===Regimen variant #3 {{#subobject:d415c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,641: | Line 4,375: | ||
{{#lst:Allogeneic HSCT|d415c}} | {{#lst:Allogeneic HSCT|d415c}} | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [http://www.bbmt.org/article/S1083-8791(08)00118-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18489993 Pubmed] | #Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [http://www.bbmt.org/article/S1083-8791(08)00118-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18489993 Pubmed] | ||
#'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23129746 PubMed] NCT00774280 | #'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23129746 PubMed] NCT00774280 | ||
#'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957 | #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957 | ||
− | |||
==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}== | ==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:a408ed|Variant=1}}=== | ===Regimen {{#subobject:a408ed|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,663: | Line 4,394: | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |} | + | |} |
− | ''Limited details are available in the abstract. Treatment is meant to be given during aplasia.'' | + | ''Limited details are available in the abstract. Treatment is meant to be given during aplasia.'' |
− | ====Preceding treatment==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | + | ====Preceding treatment==== | |
− | *[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]] salvage | + | *[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]] salvage |
− | {{#lst:Allogeneic HSCT|a408ed}} | + | {{#lst:Allogeneic HSCT|a408ed}} |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Allogeneic stem cells]] | *[[Allogeneic stem cells]] | ||
− | |||
'''Stem cells transfused on day 0''' | '''Stem cells transfused on day 0''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
#'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed] | #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed] | ||
− | |||
=Relapsed or refractory, subsequent lines of therapy= | =Relapsed or refractory, subsequent lines of therapy= | ||
''Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.'' | ''Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.'' | ||
− | |||
==Azacitidine monotherapy {{#subobject:531b70|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:531b70|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:39f96a|Variant=1}}=== | ===Regimen {{#subobject:39f96a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 4,705: | Line 4,434: | ||
|} | |} | ||
''Note: CLAVELA does not contain precise dosing information for the control arm regimens.'' | ''Note: CLAVELA does not contain precise dosing information for the control arm regimens.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7 | ||
− | |||
'''28-day cycle for at least 4 cycles''' | '''28-day cycle for at least 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | |||
#Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. [http://www.bloodjournal.org/content/116/19/3735.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20664061 PubMed] | #Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. [http://www.bloodjournal.org/content/116/19/3735.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20664061 PubMed] | ||
#'''CLAVELA:''' Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. [https://doi.org/10.1200/jco.2013.52.8562 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24841975/ PubMed] NCT01147939 | #'''CLAVELA:''' Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. [https://doi.org/10.1200/jco.2013.52.8562 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24841975/ PubMed] NCT01147939 | ||
− | |||
==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}== | ==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:596d8b|Variant=1}}=== | ===Regimen {{#subobject:596d8b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 4,731: | Line 4,456: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day | *[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day | ||
**Patients with progression were allowed to increase the dose to 50 mg PO twice per day | **Patients with progression were allowed to increase the dose to 50 mg PO twice per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- This study was presented in part at the American Society of Hematology annual meeting, December 2010, Orlando, FL. --> | <!-- This study was presented in part at the American Society of Hematology annual meeting, December 2010, Orlando, FL. --> | ||
− | |||
#'''MDACC 2007-0925:''' Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. [http://www.bloodjournal.org/content/119/20/4614.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22422826 PubMed] | #'''MDACC 2007-0925:''' Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. [http://www.bloodjournal.org/content/119/20/4614.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22422826 PubMed] | ||
− | |||
=Response criteria= | =Response criteria= | ||
==NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)== | ==NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)== | ||
− | |||
#Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. [https://doi.org/10.1200/jco.1990.8.5.813 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2185339 PubMed] | #Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. [https://doi.org/10.1200/jco.1990.8.5.813 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2185339 PubMed] | ||
− | |||
==Revised International Working Group recommendations (2003)== | ==Revised International Working Group recommendations (2003)== | ||
− | |||
#Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. [https://doi.org/10.1200/jco.2003.04.036 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14673054 PubMed] | #Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. [https://doi.org/10.1200/jco.2003.04.036 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14673054 PubMed] | ||
− | |||
=Prognosis= | =Prognosis= | ||
− | |||
==Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)== | ==Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)== | ||
− | |||
− | |||
*Relapse-free interval from first complete remission | *Relapse-free interval from first complete remission | ||
**Greater than 18 months (0 points) | **Greater than 18 months (0 points) | ||
Line 4,772: | Line 4,487: | ||
**No (0 points) | **No (0 points) | ||
**Yes, autologous or allogeneic ('''2 points''') | **Yes, autologous or allogeneic ('''2 points''') | ||
− | |||
Risk stratification: | Risk stratification: | ||
− | |||
*'''1 to 6 points''': Favorable risk (1-year OS of 70%; 5-year OS of 46%) | *'''1 to 6 points''': Favorable risk (1-year OS of 70%; 5-year OS of 46%) | ||
*'''7 to 9 points''': Intermediate risk (1-year OS of 49%; 5-year OS of 18%) | *'''7 to 9 points''': Intermediate risk (1-year OS of 49%; 5-year OS of 18%) | ||
*'''10 to 14 points''': Poor risk (1-year OS of 16%; 5-year OS of 4%) | *'''10 to 14 points''': Poor risk (1-year OS of 16%; 5-year OS of 4%) | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.06.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15632409 PubMed] | #Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.06.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15632409 PubMed] | ||
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==Prognosis in cytogenetically normal AML== | ==Prognosis in cytogenetically normal AML== | ||
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#''Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome:'' Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. [https://doi.org/10.1056/NEJMoa074306 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18450602 PubMed] | #''Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome:'' Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. [https://doi.org/10.1056/NEJMoa074306 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18450602 PubMed] | ||
#''CEBPA double mutations:'' Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. [https://ashpublications.org/blood/article/113/13/3088/24746/Double-CEBPA-mutations-but-not-single-CEBPA link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19171880 PubMed] | #''CEBPA double mutations:'' Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. [https://ashpublications.org/blood/article/113/13/3088/24746/Double-CEBPA-mutations-but-not-single-CEBPA link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19171880 PubMed] | ||
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==Whole genome sequencing== | ==Whole genome sequencing== | ||
#''Seminal paper comparing WGS to cytogenetic analysis:'' Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. [https://doi.org/10.1056/nejmoa2024534 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33704937/ PubMed] | #''Seminal paper comparing WGS to cytogenetic analysis:'' Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. [https://doi.org/10.1056/nejmoa2024534 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33704937/ PubMed] | ||
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=Investigational agents= | =Investigational agents= | ||
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''These are drugs under study with at least some promising results for this disease.'' | ''These are drugs under study with at least some promising results for this disease.'' | ||
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*[[Alvocidib (Flavopiridol)]] | *[[Alvocidib (Flavopiridol)]] | ||
*[[Pracinostat (SB939)]] | *[[Pracinostat (SB939)]] | ||
Line 4,800: | Line 4,506: | ||
*[[Volasertib (BI 6727)]] | *[[Volasertib (BI 6727)]] | ||
*[[Vosaroxin (SNS 595)]] | *[[Vosaroxin (SNS 595)]] | ||
− | |||
=Additional information= | =Additional information= | ||
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[[Category:Acute myeloid leukemia regimens]] | [[Category:Acute myeloid leukemia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Acute leukemias]] | [[Category:Acute leukemias]] |
Revision as of 12:09, 16 October 2022
Section editor transclusions
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: regimens tested in specific populations have been moved to dedicated pages:
88 regimens on this page
150 variants on this page
|
Guidelines
ASH
- 2020: Sekeres et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults
ELN
- 2022: Döhner et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
Older
- 2017: Döhner et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
- 2010: Döhner et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet
ESMO
- 2020: Heuser et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 2013: Fey et al. Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
"How I Treat"
- 2020: DeWolf & Tallman How I treat relapsed or refractory AML
- 2020: DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. link to original article PubMed
- 2016: Ofran Y, Tallman MS, Rowe JM. How I treat acute myeloid leukemia presenting with preexisting comorbidities. Blood. 2016 Jul 28;128(4):488-96. Epub 2016 May 27. link to PMC article PubMed
- 2015: Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015 May 21;125(21):3246-52. Epub 2015 Mar 16. link to original article PubMed
- 2014: Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. link to original article PubMed
NCCN
Antifungal prophylaxis
Older
- 2015: Halpern et al. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia
Upfront induction therapy, standard and older "fit" patients
These are aggressive remission induction regimens given with curative intent.
7+3d (standard-dose)
7+3d: 7 days of cytarabine + 3 days of daunorubicin
AD: Ara-C (Cytarabine) & Daunorubicin
DA: Daunorubicin & Ara-C (Cytarabine)
Regimen variant #1, 700/135 (CI Ara-C)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yates et al. 1973 | NR in abstract | Non-randomized, <20 pts (RT) | ||
Rai et al. 1981 (CALGB 7421) | 1974-1975 | Phase 3 (E-esc) | 1. 7+3d; bolus Ara-C) | Seems to have superior CR rate |
2. 5+2d | Superior CR rate | |||
3. 5+2d; bolus Ara-C | Superior CR rate | |||
Omura et al. 1982 | 1974-1975 | Phase 3 (E-de-esc) | 1. AVML | Not directly compared |
2. TAD | Superior time to CR | |||
Yates et al. 1982 (CALGB 7721) | 1977-1979 | Phase 3 (C) | 1. 7+3d (low-dose) | Did not meet efficacy endpoints |
2. 7+3a; 30 mg/m2 | Did not meet efficacy endpoints | |||
Vogler et al. 1984 | 1977-1981 | Non-randomized portion of RCT | ||
Preisler et al. 1987 (CALGB 7921) | 1979-1982 | Phase 3 (C) | 1. 10+3d | Did not meet primary endpoint of CR rate |
2. TAD | Did not meet primary endpoint of CR rate | |||
Stein et al. 1990 | 1982-1985 | Phase 3 (C) | MA | Did not meet primary endpoint of CR rate |
Arlin et al. 1990 | NR in abstract | Phase 3 (C) | 7+3m | Did not meet efficacy endpoints |
Dillman et al. 1991 (CALGB 8321) | 1982-1986 | Phase 3 (C) | 7+3d; higher-dose Ara-C | Did not meet primary efficacy endpoints |
Wiernik et al. 1992 | 1985-1989 | Phase 3 (C) | 7+3i | Seems to have inferior OS |
Vogler et al. 1992 | 1985-1989 | Phase 3 (C) | 7+3i | Seems to have inferior CR rate |
Rowe et al. 2004 (ECOG E3993) | 1993-1997 | Phase 3 (C) | 1. 7+3d & GM-CSF 2. 7+3i 3. 7+3i & GM-CSF 4. 7+3m 5. 7+3m & GM-CSF |
Did not meet primary endpoint of CR rate |
Latagliata et al. 2008 (GIMEMA GSI 103 AMLE) | 2001-2004 | Phase 3 (C) | 7+3 (Daunoxome) | Did not meet primary endpoint of CR rate |
Cripe et al. 2010 (ECOG E3999) | 2002-2005 | Phase 3 (C) | 7+3d & Zosuquidar | Did not meet primary endpoint of OS |
Fernandez et al. 2009 (ECOG E1900) | 2002-2008 | Phase 3 (C) | 7+3d; high-dose | Inferior OS |
Dombret et al. 2015 (AZA-AML-001) | 2010-2014 | Phase 3 (C) | Azacitidine | Might have inferior OS |
Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 to 3
7-day course
Subsequent treatment
- ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of 7+3i
Regimen variant #2, 700/150 (CI Ara-C)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bishop et al. 1990 | 1984-1987 | Phase 3 (C) | ADE; standard-dose | Did not meet endpoint of OS |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV bolus once per day on days 1 to 3
7-day course
Regimen variant #3, 1120/120 (intermittent Ara-C)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Masaoka et al. 1996 | NR in abstract | Randomized Phase 2 (E-switch-ic) | 7+3i | Seems to have inferior CR rate |
Chemotherapy
- Cytarabine (Ara-C) 80 mg/m2 IV over 2 hours every 12 hours on days 1 to 7
- Daunorubicin (Cerubidine) 40 mg/m2 IV bolus once per day on days 1 to 3
7-day course
Regimen variant #4, 1400/135 (CI Ara-C)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dillman et al. 1991 (CALGB 8321) | 1982-1986 | Phase 3 (E-esc) | 7+3d; lower-dose Ara-C | Did not meet primary efficacy endpoints |
Weick et al. 1996 | 1986-1991 | Phase 3 (C) | HiDAC+3d | Seems to have inferior RFS |
Zittoun et al. 1996 (AML 8B) | 1986-1993 | Phase 3 (C) | 7+3d & GM-CSF | Did not meet primary efficacy endpoint |
Moore et al. 2004 (CALGB 9222) | 1992-1995 | Non-randomized portion of phase 3 RCT | ||
Anderson et al. 2002 (SWOG S9333) | 1995-1998 | Phase 3 (C) | ME | Did not meet primary endpoint of CR rate |
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | 2000-2006 | Phase 3 (C) | 7+3d; high-dose | Inferior CR rate |
Lee et al. 2011 (ADcomparison) | 2001-2008 | Phase 3 (C) | 7+3d; high-dose | Seems to have inferior OS |
Stone et al. 2015 (ACCEDE) | 2008-2010 | Phase 3 (C) | Amonafide & Cytarabine | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 to 3
7-day course
Subsequent treatment
- CALGB 9222: HiDAC versus multi-agent chemotherapy consolidation
- HOVON 43 AML/SAKK 30/01: MiDAC consolidation
- ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise HiDAC if younger than 60 or MiDAC if greater than or equal to 60.
References
- Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. PubMed
- CALGB 7421: Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. link to original article contains dosing details in manuscript PubMed
- Omura GA, Vogler WR, Lefante J, Silberman H, Knospe W, Gordon D, Jarrell R. Treatment of acute myelogenous leukemia: influence of three induction regimens and maintenance with chemotherapy or BCG immunotherapy. Cancer. 1982 Apr 15;49(8):1530-6. link to original article contains dosing details in manuscript PubMed
- CALGB 7721: Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, James GW, Falkson G, Silver RT, Haurani F, Green M, Henderson E, Leone L, Holland JF. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood. 1982 Aug;60(2):454-62. link to original article contains dosing details in manuscript PubMed
- Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L; SECSG. A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial. Blood. 1984 May;63(5):1039-45. link to original article PubMed
- CALGB 7921: Preisler H, Davis RB, Kirshner J, Dupre E, Richards F 3rd, Hoagland HC, Kopel S, Levy RN, Carey R, Schulman P, Gottlieb AJ, McIntyre OR. Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a Cancer and Leukemia Group B study. Blood. 1987 May;69(5):1441-9. link to original article contains dosing details in manuscript PubMed
- Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A; Southeastern Cancer Study Group. Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial. Leuk Res. 1990;14(10):895-903. link to original article PubMed
- Bishop JF, Lowenthal RM, Joshua D, Matthews JP, Todd D, Cobcroft R, Whiteside MG, Kronenberg H, Ma D, Dodds A, Herrmann R, Szer J, Wolf MM, Young G; Australian Leukemia Study Group. Etoposide in acute nonlymphocytic leukemia. Blood. 1990 Jan 1;75(1):27-32. link to original article contains dosing details in abstract PubMed
- Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. PubMed
- CALGB 8321: Dillman RO, Davis RB, Green MR, Weiss RB, Gottlieb AJ, Caplan S, Kopel S, Preisler H, McIntyre OR, Schiffer C. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood. 1991 Nov 15;78(10):2520-6. link to original article contains dosing details in manuscript PubMed
- Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. link to original article contains dosing details in manuscript PubMed
- Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. link to original article contains dosing details in abstract PubMed
- AML 8B: Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, Hayat M, Peetermans M, Cadiou M, Solbu G, Petti MC, Willemze R. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996 Jul;14(7):2150-9. link to original article contains dosing details in manuscript PubMed NCT01324063
- Update: Hengeveld M, Suciu S, Karrasch M, Specchia G, Marie JP, Muus P, Petti MC, Rotoli B, Amadori S, Fioritoni G, Leoni P, Morra E, Thaler J, Resegotti L, Fazi P, Vignetti M, Mandelli F, Zittoun R, de Witte T; EORTC; GIMEMA. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organisation for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. Ann Hematol. 2012 Jun;91(6):825-35. Epub 2012 Mar 31. link to original article link to PMC article contains dosing details in abstract PubMed
- Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. contains dosing details in abstract PubMed
- Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M; SWOG. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51. link to original article contains dosing details in abstract PubMed
- SWOG S9333: Anderson JE, Kopecky KJ, Willman CL, Head D, O'Donnell MR, Luthardt FW, Norwood TH, Chen IM, Balcerzak SP, Johnson DB, Appelbaum FR. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002 Dec 1;100(12):3869-76. Epub 2002 Aug 1. link to original article contains dosing details in abstract PubMed
- ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052
- CALGB 9222: Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. link to original article link to PMC article contains dosing details in manuscript PubMed
- GIMEMA GSI 103 AMLE: Latagliata R, Breccia M, Fazi P, Iacobelli S, Martinelli G, Di Raimondo F, Sborgia M, Fabbiano F, Pirrotta MT, Zaccaria A, Amadori S, Caramatti C, Falzetti F, Candoni A, Mattei D, Morselli M, Alimena G, Vignetti M, Baccarani M, Mandelli F. Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia. Br J Haematol. 2008 Dec;143(5):681-9. Epub 2008 Oct 20. link to original article contains dosing details in manuscript PubMed
- HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology; AMLSG; Swiss Group for Clinical Cancer Research. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
- ECOG E1900: Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00049517
- Update: Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. link to original article link to PMC article PubMed
- ECOG E3999: Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Luger S, Tallman MS. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood. 2010 Nov 18;116(20):4077-85. Epub 2010 Aug 17. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00046930
- ADcomparison: Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. Epub 2011 Aug 9. link to original article contains dosing details in abstract PubMed NCT00474006
- ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637
- AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01074047
- Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
7+3d (intermediate-dose)
7+3d: 7 days of cytarabine + 3 days of daunorubicin
Regimen variant #1, CI Ara-C (100 mg/m2)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Büchner et al. 2012 (OSHO 061) | 2002-2008 | Phase 3 (C) | See paper for details | Did not meet primary endpoint of EFS |
Schaich et al. 2013 (AML2003) | 2003-2009 | Non-randomized portion of phase 3 RCT | ||
Walker et al. 2021 (CALGB 10201) | 2004-2006 | Phase 3 (C) | 7+3d & Oblimersen | Did not meet primary endpoint of OS |
Petersdorf et al. 2013 (SWOG S0106) | 2004-2009 | Phase 3 (C) | 7+3d & GO | Did not meet primary endpoint of CR rate |
Serve et al. 2013 (AML2006) | 2006-2008 | Randomized Phase 2 (C) | 7+3d & Sorafenib | Did not meet primary endpoint of EFS |
Röllig et al. 2015 (SORAML) | 2009-2011 | Randomized Phase 2 (C) | 7+3d & Sorafenib | Seems to have inferior EFS |
Müller-Tidow et al. 2015 (AML-AZA) | 2010-2012 | Phase 3 (C) | 7+3d & Azacitidine | Did not meet primary endpoint of EFS |
Dombret et al. 2015 (AZA-AML-001) | 2010-2014 | Phase 3 (C) | Azacitidine | Might have inferior OS |
Lancet et al. 2018 (CLTR0310-301) | 2012-2014 | Phase 3 (C) | CPX-351 | Inferior OS |
Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
- Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5
7-day course
Subsequent treatment
- AML2003: HiDAC versus MAC/MAMAC/MAC consolidation
- CALGB 10201: IDAC consolidation x 2
- SWOG S0106: HiDAC consolidation x 3
- CLTR0310-301: 5+2d consolidation
Regimen variant #2, CI Ara-C (200 mg/m2)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Holowiecki et al. 2004 (PALG AML1/1999) | 1999-2002 | Phase 3 (C) | DAC | Inferior CR rate after first induction |
Chevallier et al. 2010 (LAM-2001) | 2001-2005 | Phase 3 (C) | 7+5i | Did not meet primary endpoint of LFS |
Holowiecki et al. 2012 (PALG AML1/2004) | 2004-2008 | Phase 3 (C) | 1. DAC | Inferior OS |
2. DAF | Seems to have inferior OS | |||
Castaigne et al. 2012 (ALFA-0701) | 2008-2010 | Phase 3 (C) | 7+3d & GO | Inferior EFS |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
Supportive therapy
- "According to commonly accepted guidelines with no prophylactic IV antibiotics"
- Granulocyte colony-stimulating factor recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
7-day course
Subsequent treatment
- Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule.
- PALG AML1/1999, non-responders: CLAG salvage
- Patients in remission in both PALG studies: HAM, then HiDAC consolidation
- ALFA-0701, CR or CRp: Cytarabine & daunorubicin consolidation
References
- PALG AML1/1999: Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. link to original article contains dosing details in manuscript PubMed
- LAM-2001: Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. link to original article contains dosing details in abstract PubMed
- Update: Récher C, Béné MC, Lioure B, Pigneux A, Vey N, Delaunay J, Luquet I, Hunault M, Guyotat D, Bouscary D, Fegueux N, Jourdan E, Lissandre S, Escoffre-Barbe M, Bonmati C, Randriamalala E, Guièze R, Ojeda-Uribe M, Dreyfus F, Harousseau JL, Cahn JY, Ifrah N, Guardiola P; Groupe Ouest-Est d’ étude des Leucé mies Aiguës et autres. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia. Leukemia. 2014 Feb;28(2):440-3. Epub 2013 Oct 9. link to original article PubMed
- PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
- ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. Epub 2012 Apr 5. link to original article contains dosing details in manuscript PubMed NCT00927498
- Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
- OSHO 061: Büchner T, Schlenk RF, Schaich M, Döhner K, Krahl R, Krauter J, Heil G, Krug U, Sauerland MC, Heinecke A, Späth D, Kramer M, Scholl S, Berdel WE, Hiddemann W, Hoelzer D, Hehlmann R, Hasford J, Hoffmann VS, Döhner H, Ehninger G, Ganser A, Niederwieser DW, Pfirrmann M. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol. 2012 Oct 10;30(29):3604-10. Epub 2012 Sep 10. link to original article contains dosing details in manuscript PubMed NCT01414231
- AML2003: Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. link to original article contains dosing details in manuscript PubMed NCT00180102
- AML2006: Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, Schaich M, Ottmann O, Duyster J, Wandt H, Fischer T, Giagounidis A, Neubauer A, Reichle A, Aulitzky W, Noppeney R, Blau I, Kunzmann V, Stuhlmann R, Krämer A, Kreuzer KA, Brandts C, Steffen B, Thiede C, Müller-Tidow C, Ehninger G, Berdel WE. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013 Sep 1;31(25):3110-8. Epub 2013 Jul 29. link to original article contains dosing details in abstract PubMed NCT00373373
- SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article PubMed NCT00085709
- AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01074047
- Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
- AML-AZA: Müller-Tidow C, Tschanter P, Röllig C, Thiede C, Koschmieder A, Stelljes M, Koschmieder S, Dugas M, Gerss J, Butterfaß-Bahloul T, Wagner R, Eveslage M, Thiem U, Krause SW, Kaiser U, Kunzmann V, Steffen B, Noppeney R, Herr W, Baldus CD, Schmitz N, Götze K, Reichle A, Kaufmann M, Neubauer A, Schäfer-Eckart K, Hänel M, Peceny R, Frickhofen N, Kiehl M, Giagounidis A, Görner M, Repp R, Link H, Kiani A, Naumann R, Brümmendorf TH, Serve H, Ehninger G, Berdel WE, Krug U; Study Alliance Leukemia Group. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia. Leukemia. 2016 Mar;30(3):555-61. Epub 2015 Nov 2. link to original article contains dosing details in manuscript PubMed NCT00915252
- SORAML: Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. link to original article PubMed NCT00893373
- CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
- Update: Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. link to original article PubMed
- CALGB 10201: Walker AR, Marcucci G, Yin J, Blum W, Stock W, Kohlschmidt J, Mrózek K, Carroll AJ, Eisfeld AK, Wang ES, Jacobson S, Kolitz JE, Thakuri M, Sutamtewagul G, Vij R, Stuart RK, Byrd JC, Bloomfield CD, Stone RM, Larson RA. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance). Blood Adv. 2021 Jul 13;5(13):2775-2787. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00085124.
- AMLSG31-19: NCT04628026
- ECOG E2906: NCT02085408
- ENHANCE-2: NCT04778397
7+3d (high-dose)
7+3d: 7 days of cytarabine + 3 days of daunorubicin
Regimen variant #1, 700/270
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fernandez et al. 2009 (ECOG E1900) | 2002-2008 | Phase 3 (E-esc) | 7+3d; standard-dose | Superior OS Median OS: 23.7 vs 15.7 mo (HR 0.74, 95% CI 0.60-0.90) |
Zeidner et al. 2015 (JHOC-J1101) | 2011-2013 | Randomized Phase 2 (C) | FLAM | Inferior CR rate |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 90 mg/m2 IV once per day on days 1 to 3
7-day course
Subsequent treatment
- JHOC-J1101: Patients with residual leukemia at day 14 underwent 5+2d salvage
Regimen variant #2, 1400/240
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Castaigne et al. 2004 (ALFA 9000) | 1990-1996 | Phase 3 (C) | 1. 7+3d x 2 2. Timed sequential induction |
Did not meet primary endpoint of RFI |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Daunorubicin (Cerubidine) 80 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen variant #3, 1400/270
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | 2000-2006 | Phase 3 (E-esc) | 7+3d; standard-dose | Superior CR rate |
Lee et al. 2011 (ADcomparison) | 2001-2008 | Phase 3 (E-esc) | 7+3d; standard-dose | Seems to have superior OS OS60: 46.8% vs 34.6% (HR 0.74, 95% CI 0.58-0.97) |
Lee et al. 2017 (COSAH C-022) | 2010-2014 | Phase 3 (C) | 7+3i | Inconclusive whether non-inferior CR rate |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Daunorubicin (Cerubidine) 90 mg/m2 IV once per day on days 1 to 3
7-day course
Subsequent treatment
- HOVON 43 AML/SAKK 30/01: MiDAC consolidation
- COSAH C-022, with CR, good- or intermediate-risk cytogenetics: HiDAC consolidation
- COSAH C-022, with CR, high-risk cytogenetics: Cytarabine & etoposide consolidation
References
- ALFA 9000: Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. link to original article contains dosing details in manuscript PubMed
- HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
- ECOG E1900: Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00049517
- Update: Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. link to original article link to PMC article PubMed
- ADcomparison: Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. Epub 2011 Aug 9. link to original article contains dosing details in abstract PubMed NCT00474006
- JHOC-J1101: Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01349972
- COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846
7+3d & GO
7+3d & GO: 7 days of Cytarabine, 3 days of daunorubicin, Gemtuzumab Ozogamicin
Regimen variant #1, split GO dosing
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Castaigne et al. 2012 (ALFA-0701) | 2008-2010 | Phase 3 (E-RT-esc) | 7+3d; intermediate-dose | Seems to have superior OS OS24: 53.2% vs 41.9% (HR 0.69, 95% CI 0.49-0.98) |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7
7-day course
Subsequent treatment
- Patients in CR or CRp and platelet count at least 100 x 109 by day 45 after the initiation of chemotherapy: Cytarabine, Daunorubicin, Gemtuzumab ozogamicin consolidation
- Patients in CR or CRp and platelet count less than 100 x 109 by day 45 after the initiation of chemotherapy: Cytarabine & Daunorubicin consolidation
Regimen variant #2, single-day GO
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Petersdorf et al. 2013 (SWOG S0106) | 2004-2009 | Phase 3 (E-esc) | 7+3d; intermediate-dose | Did not meet primary endpoint of CR rate |
Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 to 3
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 6 mg/m2 IV over 2 hours once on day 4
7-day course
Subsequent treatment
- HiDAC consolidation x 3
References
- ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
- Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
- SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00085709
7+3i
7+3i: 7 days of cytarabine + 3 days of idarubicin
AI: Ara-C (Cytarabine) & Idarubicin
IA: Idarubicin & Ara-C (Cytarabine)
Regimen variant #1, 80/12, intermittent Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Masaoka et al. 1996 | NR in abstract | Randomized Phase 2 (E-switch-ic) | 7+3d; standard-dose | Seems to have superior CR rate |
Chemotherapy
- Cytarabine (Ara-C) 80 mg/m2 IV over 2 hours every 12 hours on days 1 to 7
- Idarubicin (Idamycin) 12 mg/m2 IV bolus once per day on days 1 to 3
7-day course
Regimen variant #2, 100/12, CI Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mandelli et al. 1991 | 1984-1987 | Phase 3 (E-RT-switch-ic) | 7+3d | Did not meet primary endpoint of FFS |
Vogler et al. 1992 | 1985-1989 | Phase 3 (E-RT-switch-ic) | 7+3d | Seems to have superior CR rate |
Haas et al. 1993 | 1989-NR | Non-randomized | ||
Rowe et al. 2004 (ECOG E3993) | 1993-1997 | Phase 3 (E-switch-ic) | 1. 7+3d; standard-dose 2. 7+3d + GM-CSF 3. 7+3i + GM-CSF 4. 7+3m 5. 7+3m + GM-CSF |
Did not meet primary endpoint of CR rate |
Ohtake et al. 2010 (JALSG AML95) | 1995-1997 | Phase 3 (C) | Individualized chemotherapy | Did not meet efficacy endpoints |
Miyawaki et al. 2005 (JALSG AML97) | 1997-2001 | Non-randomized portion of RCT | ||
Ohtake et al. 2010 (JALSG AML201) | 2001-2005 | Phase 3 (C) | 7+5d | Inconclusive whether non-inferior CR rate |
Note: Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Idarubicin (Idamycin) 12 mg/m2 IV once per day on days 1 to 3
7-day course (see note)
Regimen variant #3, 100/13, CI Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wiernik et al. 1992 | 1985-1989 | Phase 3 (E-RT-switch-ic) | 7+3d; standard-dose | Seems to have superior OS |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Idarubicin (Idamycin) 13 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen variant #4, 200/12, CI Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Löwenberg et al. 2003 (HOVON/SAKK AML 29) | 1995-1999 | Phase 3 (C) | 7+3i & G-CSF | Seems to have inferior DFS |
Pautas et al. 2010 (ALFA-9801) | 1999-2006 | Phase 3 (C) | 1. 7+3d; high-dose 2. 7+4i |
Did not meet primary endpoint of EFS |
Löwenberg et al. 2011 (HOVON/SAKK AML 42) | 2001-2006 | Phase 3 (C) | HiDAC+3i | Did not meet primary endpoint of EFS |
Löwenberg et al. 2017 (HOVON-102) | 2010-2013 | Phase 3 (C) | 7+3i & Clofarabine | Did not meet primary endpoint of EFS |
Lee et al. 2017 (COSAH C-022) | 2010-2014 | Phase 3 (C) | 7+3d; high-dose | Inconclusive whether non-inferior CR rate |
Löwenberg et al. 2021 (HOVON/SAKK-132) | 2015-2017 | Phase 3 (C) | 7+3i & Lenalidomide | Did not meet primary endpoint of EFS |
Chemotherapy
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Idarubicin (Idamycin) 12 mg/m2 IV over 3 hours once per day on days 1 to 3
- Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7
7-day course
Subsequent treatment
- HOVON/SAKK AML 29 & AML 42: Amsacrine & Cytarabine
- ALFA-9801, patients achieiving CR: cytarabine & idarubicin consolidation
- COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: HiDAC consolidation
- COSAH C-022, patients achieving CR, high-risk cytogenetics: CYVE consolidation
- HOVON/SAKK-132: Daunorubicin & IDAC (remission induction cycle II)
Regimen variant #5, with range
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dombret et al. 2015 (AZA-AML-001) | 2010-2014 | Phase 3 (C) | Azacitidine | Might have inferior OS |
Chemotherapy
- Cytarabine (Ara-C) 100 to 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m2)
- Idarubicin (Idamycin) 9 to 12 mg/m2 IV once per day on days 1 to 3
7-day course
References
- Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. link to original article PubMed
- Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. link to original article contains dosing details in manuscript PubMed
- Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. link to original article contains dosing details in abstract PubMed
- Haas R, Ho AD, Del Valle F, Fischer JT, Ehrhardt R, Döhner H, Witt B, Huberts H, Kaplan E, Hunstein W. Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of de novo acute myelogenous leukemia. Semin Oncol. 1993 Dec;20(6 Suppl 8):20-6. PubMed
- Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. contains dosing details in abstract PubMed
- HOVON/SAKK AML 29: Löwenberg B, van Putten W, Theobald M, Gmür J, Verdonck L, Sonneveld P, Fey M, Schouten H, de Greef G, Ferrant A, Kovacsovics T, Gratwohl A, Daenen S, Huijgens P, Boogaerts M; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003 Aug 21;349(8):743-52. link to original article contains dosing details in manuscript PubMed
- ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052
- JALSG AML97: Miyawaki S, Sakamaki H, Ohtake S, Emi N, Yagasaki F, Mitani K, Matsuda S, Kishimoto Y, Miyazaki Y, Asou N, Matsushima T, Takahashi M, Ogawa Y, Honda S, Ohno R; Japan Adult Leukemia Study Group. A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 study. Cancer. 2005 Dec 15;104(12):2726-34. link to original article contains dosing details in abstract PubMed
- ALFA-9801: Pautas C, Merabet F, Thomas X, Raffoux E, Gardin C, Corm S, Bourhis JH, Reman O, Turlure P, Contentin N, de Revel T, Rousselot P, Preudhomme C, Bordessoule D, Fenaux P, Terré C, Michallet M, Dombret H, Chevret S, Castaigne S. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010 Feb 10;28(5):808-14. Epub 2010 Jan 4. link to original article contains dosing details in manuscript PubMed NCT00931138
- JALSG AML95: Ohtake S, Miyawaki S, Kiyoi H, Miyazaki Y, Okumura H, Matsuda S, Nagai T, Kishimoto Y, Okada M, Takahashi M, Handa H, Takeuchi J, Kageyama S, Asou N, Yagasaki F, Maeda Y, Ohnishi K, Naoe T, Ohno R. Randomized trial of response-oriented individualized versus fixed-schedule induction chemotherapy with idarubicin and cytarabine in adult acute myeloid leukemia: the JALSG AML95 study. Int J Hematol. 2010 Mar;91(2):276-83. link to original article contains dosing details in abstract PubMed
- JALSG AML201: Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, Okumura H, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2358-65. Epub 2010 Aug 6. link to original article PubMed C000000157
- HOVON/SAKK AML 42: Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ; HOVON; SAKK. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. link to original article contains dosing details in manuscript PubMed NTR230
- AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in abstract link to PMC article PubMed NCT01074047
- Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
- HOVON-102: Löwenberg B, Pabst T, Maertens J, van Norden Y, Biemond BJ, Schouten HC, Spertini O, Vellenga E, Graux C, Havelange V, de Greef GE, de Weerdt O, Legdeur MJ, Kuball J, Kooy MV, Gjertsen BT, Jongen-Lavrencic M, van de Loosdrecht AA, van Lammeren-Venema D, Hodossy B, Breems DA, Chalandon Y, Passweg J, Valk PJ, Manz MG, Ossenkoppele GJ; HOVON; SAKK. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML. Blood. 2017 Mar 23;129(12):1636-1645. Epub 2017 Jan 3. link to original article contains dosing details in manuscript PubMed NTR2187
- COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846
- HOVON/SAKK-132: Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. link to original article contains dosing details in manuscript link to PMC article PubMed
- SWOG S1203: NCT01802333
7+3i & Sorafenib
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Ravandi et al. 2010 (BAY43-9006) | 2007-2009 | Phase 1/2 |
Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.
Chemotherapy
- Cytarabine (Ara-C) by the following age-based criteria:
- 60 and younger: 1500 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m2)
- Older than 60: 1500 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m2)
- Idarubicin (Idamycin) 12 mg/m2 IV over 60 minutes once per day on days 1 to 3
Targeted therapy
- Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 7
7-day course
Subsequent treatment
- Cytarabine, idarubicin, sorafenib consolidation
References
- BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
- Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed
7+3d & Glasdegib
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Cortes et al. 2018 (B1371003) | 2012-NR | Phase 2 |
Note: glasdegib is continued beyond induction; see paper for details.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
Targeted therapy
- Glasdegib (Daurismo) 100 mg PO once per day, started on day -3
28-day course
Subsequent treatment
- IDAC consolidation
References
- B1371003: Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01546038
7+3m
7+3m: 7 days of cytarabine + 3 days of mitoxantrone
MAC: Mitoxantrone & Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arlin et al. 1990 | NR in abstract | Phase 3 (E-RT-switch-ic) | 7+3d | Did not meet efficacy endpoints |
Rowe et al. 2004 (ECOG E3993) | 1993-1997 | Phase 3 (E-switch-ic) | 1. 7+3d; standard-dose 2. 7+3d + GM-CSF 3. 7+3i 4. 7+3i + GM-CSF 5. 7+3m + GM-CSF |
Did not meet primary endpoint of CR rate |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Mitoxantrone (Novantrone) 12 mg/m2 IV once per day on days 1 to 3
7-day course
Subsequent treatment
- Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of 7+3m
References
- Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. PubMed
- ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052
ADE (standard-dose Ara-C)
ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
7-3-7: 7 days of Cytarabine, 3 days of Daunorubicin, 7 days of Etoposide
8-3-5: 8 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide
10-3-5: 10 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide
Regimen variant #1, 7-3-7, 700/150/525
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bishop et al. 1996 | 1987-1991 | Phase 3 (C) | ADE (high-dose Ara-C) | Inferior DFS |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 7
7-day course; can be repeated up to 3 times if CR not achieved
Subsequent treatment
- 5-2-5 consolidation x 2
Regimen variant #2, 7-3-3, 700/180/300
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baer et al. 2002 (CALGB 9720) | 1998-1999 | Phase 3 (C) | ADEP | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen variant #3, 7-3-3, 700/270/300
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kolitz et al. 2010 (CALGB 19808) | 2001-2003 | Phase 3 (C) | ADEP | Did not meet primary endpoints of DFS/OS |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 90 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Willemze et al. 2013 (EORTC-GIMEMA AML-12) | 1999-2008 | Phase 3 (C) | ADE (high-dose Ara-C) | Seems to have inferior OS |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 10 days, started on day 1 (total dose: 1000 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV over 5 minutes once per day on days 1, 3, 5
- Etoposide (Vepesid) 50 mg/m2 IV over 60 minutes once per day on days 1 to 5
10-day course
Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mandelli et al. 2009 (EORTC-GIMEMA AML-10) | 1993-1999 | Phase 3 (C) | 1. AIE 2. AME |
Did not meet primary endpoint of OS |
Chemotherapy
- Cytarabine (Ara-C) 25 mg/m2/day IV bolus once on day 1, then 100 mg/m2/day IV continuous infusion over 10 days (total dose: 1025 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV over 5 minutes once per day on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
10-day course
Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hann et al. 1997 (UK MRC AML10) | 1988-1995 | Phase 3 (E-switch-ic) | DAT 3+8 | Did not meet efficacy endpoints |
Burnett et al. 2010 (UK MRC AML15) | 2002-2006 | Phase 3 (C) | See link | See link |
Note: these trials have complicated treatment schemas; see papers for details.
Preceding treatment
- UK MRC AML10: ADE 10-3-5 induction
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV every 12 hours on days 1 to 8
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
8-day course
Subsequent treatment
- UK MRC AML10: MACE consolidation
- UK MRC AML15: Consolidation (see paper for details)
Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hann et al. 1997 (UK MRC AML10) | 1988-1995 | Phase 3 (E-switch-ic) | DAT 3+10 | Did not meet efficacy endpoints |
Burnett et al. 1999 (UK MRC AML12) | 1993-1997 | Phase 3 (C) | See link | See link |
Burnett et al. 2010 (UK MRC AML15) | 2002-2006 | Phase 3 (C) | See link | See link |
Note: these trials have complicated treatment schemas; see papers for details.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV every 12 hours on days 1 to 10
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
10-day course
Subsequent treatment
- ADE 8-3-5 re-induction
References
- Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. link to original article contains dosing details in abstract PubMed
- UK MRC AML10: Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. link to original article contains dosing details in manuscript PubMed
- Update: Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, Wheatley K; UK Medical Research Council Adult and Children's Leukaemia Working Parties. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet. 1998 Mar 7;351(9104):700-8. link to original article PubMed
- UK MRC AML12: Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. link to original article PubMed NCT00002658
- Update: Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. Epub 2009 Dec 28. link to original article PubMed
- CALGB 9720: Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002 Aug 15;100(4):1224-32. link to original article contains dosing details in abstract PubMed NCT00003190
- Update: Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K, Kolitz JE, Powell BL, Moore JO, Stone RM, Anastasi J, Bloomfield CD, Larson RA. Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720. J Clin Oncol. 2008 Oct 20;26(30):4934-9. Epub 2008 Jun 30. link to original article link to PMC article PubMed
- EORTC-GIMEMA AML-10: Mandelli F, Vignetti M, Suciu S, Stasi R, Petti MC, Meloni G, Muus P, Marmont F, Marie JP, Labar B, Thomas X, Di Raimondo F, Willemze R, Liso V, Ferrara F, Baila L, Fazi P, Zittoun R, Amadori S, de Witte T; EORTC; GIMEMA. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol. 2009 Nov 10;27(32):5397-403. Epub 2009 Oct 13. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1438. link to original article link to PMC article PubMed
- Update: Baron F, Efficace F, Cannella L, Muus P, Trisolini S, Halkes CJM, Fazi P, Vignetti M, Marie JP, Chiusolo P, van der Velden W, La Sala E, Vitolo U, Thomas X, Lefrère F, Di Raimondo F, Bourhis JH, Specchia G, Guimarães JE, Allione B, Vrhovac R, Ferrara F, Stevens-Kroef M, Meert L, de Witte T, Willemze R, Amadori S, Suciu S. Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study. Am J Hematol. 2020 Jul;95(7):749-758. Epub 2020 Apr 17. link to original article PubMed
- CALGB 19808: Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. Epub 2010 Jun 3. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00006363
- UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
- Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
- Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
- EORTC-GIMEMA AML-12: Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. link to original article contains dosing details in manuscript PubMed NCT00004128
ADE (high-dose Ara-C)
ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
HIDAC-3-5: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 5 days of Etoposide
HIDAC-3-7: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 7 days of Etoposide
Regimen variant #1, HIDAC-3-5
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Willemze et al. 2013 (EORTC-GIMEMA AML-12) | 1999-2008 | Phase 3 (E-esc) | ADE (standard-dose Ara-C) | Seems to have superior OS OS72: 42.5% vs 38.7% (HR 0.89, 95% CI 0.79-1.00) |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV over 5 minutes once per day on days 1, 3, 5
- Etoposide (Vepesid) 50 mg/m2 IV over 60 minutes once per day on days 1 to 5
7-day course
Regimen variant #2, HIDAC-3-7
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bishop et al. 1996 | 1987-1991 | Phase 3 (E-esc) | ADE (standard-dose Ara-C) | Superior DFS |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 7
7-day course; can be repeated up to 3 times if CR not achieved
Subsequent treatment
- 5-2-5 consolidation x 2
References
- Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. link to original article contains dosing details in abstract PubMed
- EORTC-GIMEMA AML-12: Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. link to original article contains dosing details in manuscript PubMed NCT00004128
AIE
AIE: Ara-C (Cytarabine), Idarubicin, Etoposide
ICE: Idarubicin, Cytarabine, Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bradstock et al. 2004 (ALLG M7) | 1995-2000 | Non-randomized portion of RCT | ||
de Witte et al. 2010 (CRIANT) | 1996-2003 | Non-randomized portion of phase 3 RCT | ||
Schlenk et al. 2004 | 1998-2001 | Phase 3 (C) | A-ICE | Inferior OS |
Russo et al. 2005 | 1999-2002 | Phase 3 (C) | FLAI | Inferior CR rate |
Bassan et al. 2019 (NILG AML 02/06) | 2007-2012 | Phase 3 (C) | Sequential high-dose therapy | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m2)
- Idarubicin (Idamycin) 12 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
7-day course
Subsequent treatment
- ALLG M7: ICE versus IcE consolidation
- NILG AML 02/06, early CR: IC consolidation
References
- ALLG M7: Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. link to original article PubMed
- Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. link to original article PubMed
- Russo D, Malagola M, de Vivo A, Fiacchini M, Martinelli G, Piccaluga PP, Damiani D, Candoni A, Michielutti A, Castelli M, Testoni N, Ottaviani E, Rondoni M, Pricolo G, Mazza P, Zuffa E, Zaccaria A, Raspadori D, Bocchia M, Lauria F, Bonini A, Avanzini P, Gugliotta L, Visani G, Fanin R, Baccarani M. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol. 2005 Oct;131(2):172-9. Erratum in: Br J Haematol. 2006 Mar;132(6):804. link to original article PubMed
- CRIANT: de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellström-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. Epub 2010 May 21. link to original article link to PMC article PubMed NCT00002926
- NILG AML 02/06: Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00495287
CIA
CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)
Regimen variant #1, 15/10/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jabbour et al. 2017 (MDACC 2010-0788) | 2011-2016 | Randomized Phase 2 (E-switch-ic) | FIA | Did not meet primary endpoint of EFS |
Chemotherapy
- Clofarabine (Clolar) 15 mg/m2 IV once per day on days 1 to 5, given 4 hours before cytarabine
- Idarubicin (Idamycin) 10 mg/m2 IV once per day on days 1 to 3
- Cytarabine (Ara-C) 1000 mg/m2 IV over 2 hours once per day on days 1 to 5
5-day course
Regimen variant #2, 20/10/1000
Study | Years of enrollment | Evidence |
---|---|---|
Nazha et al. 2013 | 2010-2012 | Phase 2 |
Chemotherapy
- Clofarabine (Clolar) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Idarubicin (Idamycin) 10 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Cytarabine (Ara-C) 1000 mg/m2 IV over 2 hours once per day on days 1 to 5
Supportive therapy
- Levofloxacin (Levaquin)
- Itraconazole (Sporanox)
- Valacyclovir (Valtrex)
- Granulocyte colony-stimulating factor neither mandated nor forbidden and given per physician discretion
5-day course
Subsequent treatment
- Patients with PR: a second course with the same drugs, doses, and schedule.
- Patients achieving CR or CRi: CIA consolidation
References
- Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. long link to original article contains dosing details in manuscript link to PMC article PubMed
- MDACC 2010-0788: Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01289457
DA 3 + 10
DA 3 + 10: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine
Regimen variant #1, 50 mg/m2 dauno
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2010 (UK MRC AML15) | 2002-2006 | Phase 3 (C) | See link | See link |
Burnett et al. 2012 (UK NCRI AML16) | 2006-2010 | Phase 3 (C) | DA 3 + 10, GO | Seems to have inferior OS |
Note: this regimen is very similar to 7+3d; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 10
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
10-day course
Subsequent treatment
- See papers for details (to be completed).
Regimen variant #2, 60 mg/m2 dauno
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2015 (UK NCRI AML17) | 2011-2013 | Phase 3 (C) | DA 3 + 10; high-dose | Did not meet primary endpoint of OS |
Note: this regimen is very similar to 7+3d; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 10
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1, 3, 5
10-day course
Subsequent treatment
- CBF: DA 3+8 & GO
- Non-CBF, no FLT3 mutation, not poor risk: DA 3+8 versus DA 3+8 & Everolimus
- Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus FLAG-Ida
References
- UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
- Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
- Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
- UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
- Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
- Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
- UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
- Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed
DA 3 + 10, GO
DA 3 + 10, GO: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine, Gemtuzumab Ozogamicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2010 (UK MRC AML15) | 2002-2006 | Phase 3 (E-esc) | See link | See link |
Burnett et al. 2012 (UK NCRI AML16) | 2006-2010 | Phase 3 (E-esc) | DA 3 + 10 | Seems to have superior OS OS36: 25% vs 20% (HR 0.87, 95% CI 0.76-1.00) |
Note: Both trials have complicated treatment schemas; see papers for details.
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 10
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 1
10-day course
Subsequent treatment
- See paper for details (to be completed).
References
- UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
- Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
- Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
- UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
- Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
- Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
DAC
DAC: Daunorubicin, Ara-C (Cytarabine), Cladribine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Holowiecki et al. 2004 (PALG AML1/1999) | 1999-2002 | Phase 3 (E-esc) | DA | Superior CR rate after first induction |
Holowiecki et al. 2012 (PALG AML1/2004) | 2004-2008 | Phase 3 (E-esc) | 1. DA | Superior OS Median OS: 24 vs 14 mo (HR 0.69, 97.5% CI 0.5-0.96) |
2. DAF | Seems to have superior OS |
Chemotherapy
- Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
- Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
- Cladribine (Leustatin) 5 mg/m2 IV over 3 hours once per day on days 1 to 5
Supportive therapy
- "According to commonly accepted guidelines with no prophylactic IV antibiotics"
- Granulocyte colony-stimulating factor recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
7-day course
References
- PALG AML1/1999: Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. link to original article contains dosing details in manuscript PubMed
- PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
FLAG-Ida
FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Lenograstim), Idarubicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2010 (UK MRC AML15) | 2002-2006 | Phase 3 (C) | 1. ADE 10+3+5 2. DA 3+10 3. DA 3+10 & GO 4. FLAG-Ida & GO |
Did not meet primary endpoint of OS1 |
1While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days 2 to 6
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 2 to 6, given 4 hours after fludarabine
- Idarubicin (Idamycin) 8 mg/m2 IV once per day on days 4 to 6
Growth factor therapy
- Lenograstim (Granocyte) 263 mcg SC once per day on days 1 to 7
7-day course
Subsequent treatment
- See paper for details
References
- UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
- Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
- Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
HAA
HAA: Homoharringtonine (Omacetaxine), Ara-C (Cytarabine), Aclarubicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jin et al. 2013 | 2007-2011 | Phase 3 (E-esc) | 1. DA | Superior EFS |
2. HAD | Not reported |
Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.
Chemotherapy
- Omacetaxine (Synribo) 2 mg/m2/day (route not specified) on days 1 to 7
- Cytarabine (Ara-C) 100 mg/m2 IV once per day on days 1 to 7
- Aclarubicin (Aclacinon) 20 mg IV once per day on days 1 to 7
7-day course
Subsequent treatment
- Patient in CR: IDAC consolidation x 2
References
- Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. link to original article contains dosing details in abstract PubMed ChiCTR-TRC-06000054
ICL
ICL: Idarubicin, Cytarabine, Lomustine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pigneux et al. 2017 (LAM-SA 2007) | 2008-2011 | Phase 3 (E-esc) | IA | Seems to have superior OS OS24: 56% vs 48% (HR 0.73, 95% CI 0.54-0.99) |
Chemotherapy
- Idarubicin (Idamycin) 8 mg/m2 IV once per day on days 1 to 5
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
- Lomustine (CCNU) 200 mg/m2 PO once on day 1
7-day course
Subsequent treatment
References
- LAM-SA 2007: Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. link to original article contains dosing details in manuscript PubMed NCT00590837
MEC
MEC: Mitoxantrone, Etoposide, Cytarabine
MICE: MItoxantrone, Cytarabine, Etoposide
MAE: Mitoxantrone, Ara-C (Cytarabine), Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Amadori et al. 2005 (EORTC/GIMEMA AML-13) | 1995-2001 | Phase 3 (C) | MICE & G-CSF | Inferior CR rate |
Amadori et al. 2013 (EORTC/GIMEMA AML-17) | 2002-2007 | Phase 3 (C) | GO, then MICE | Might have superior OS Median OS: 10 vs 7.1 mo (HR 0.83, 95% CI 0.69-1.01) |
Chemotherapy
- Mitoxantrone (Novantrone) 7 mg/m2 IV once per day on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
7-day course
References
- EORTC/GIMEMA AML-13: Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; EORTC; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. link to original article link to PMC article PubMed NCT00002719
- Update: Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. link to original article PubMed
- EORTC/GIMEMA AML-17: Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. link to original article contains dosing details in manuscript PubMed NCT00052299
Subsequent induction therapy, standard and older "fit" patients
Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.
DA 3+8
DA 3+8: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2015 (UK NCRI AML17) | 2009-2012 | Phase 3 (C)]] | DA 3+8 & Everolimus | Did not meet primary endpoint of RFS |
Biomarker eligibility criteria
- Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 8
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1, 3, 5
10-day course
References
- UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
- Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed
DA 3+8 & GO
DA 3+8 & GO: Daunorubicin, Ara-C (Cytarabine), 3 days of daunorubicin + 8 days of cytarabine, Gemtuzumab Ozogamicin
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Burnett et al. 2015 (UK NCRI AML17) | 2011-2013 | Non-randomized portion of phase 3 RCT |
Biomarker eligibility criteria
- Core-binding factor (CBF) AML
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 8
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 1
8-day course
References
- UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
- Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed
First-line induction therapy, older or "unfit" patients
Note: these regimens are generally considered to be part of a non-curative line of treatment.
Azacitidine monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fenaux et al. 2009 (AZA PH GL 2003) | 2003-2007 | Phase 3 (E-esc) | Investigator's choice of: 1. Best supportive care 2. LoDAC 3. Intensive chemotherapy |
Superior OS Median OS: 24.5 vs 16 mo (HR 0.47, 95% CI 0.28-0.79) |
Dombret et al. 2015 (AZA-AML-001) | 2010-2014 | Phase 3 (E-esc) | Investigator's choice of: 1. 7+3d; standard-dose 2. 7+3d; intermediate-dose 3. 7+3i 4. Best supportive care 5. LoDAC |
Might have superior OS Median OS: 10.4 vs 6.5 mo (HR 0.85, 95% CI 0.69-1.03) |
Vives et al. 2021 (FLUGAZA) | 2014-NR in abstract | Phase 3 (E-switch-ooc) | FLUGA | Superior OS Median OS: 9.8 vs 4.1 mo |
DiNardo et al. 2020 (VIALE-A) | 2017-2019 | Phase 3 (C) | Azacitidine & Venetoclax | Inferior OS |
Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 7
28-day cycle for at least 6 cycles
References
- AZA PH GL 2003: Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. link to original article PubMed NCT00071799
- AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01074047
- Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
- VIALE-A: DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. link to original article contains dosing details in abstract PubMed NCT02993523
- FLUGAZA: Vives S, Martínez-Cuadrón D, Bergua Burgues J, Algarra L, Tormo M, Martínez-Sánchez MP, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, López-Lorenzo JL, Gil C, Vidriales B, Falantes JF, Serrano A, Labrador J, Sayas MJ, Foncillas MÁ, Amador Barciela ML, Olave MT, Colorado M, Gascón A, Fernández MÁ, Simiele A, Pérez-Encinas MM, Rodríguez-Veiga R, García O, Martínez-López J, Barragán E, Paiva B, Sanz MÁ, Montesinos P; PETHEMA Group. A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia. Cancer. 2021 Jun 15;127(12):2003-2014. Epub 2021 Feb 24. link to original article PubMed NCT02319135
- PEVOLAM: NCT04090736
- PRAN-16-52: NCT03151408
Azacitidine & Venetoclax
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
DiNardo et al. 2018 (M14-358) | 2014-2015 | Phase 1b, >20 pts (RT) | ||
DiNardo et al. 2020 (VIALE-A) | 2017-2019 | Phase 3 (E-RT-esc) | Azacitidine | Superior OS Median OS: 14.7 vs 9.6 mo (HR 0.66, 95% CI 0.52-0.85) |
Note: Patients with WBC greater than 25 x 109/L at presentation were pre-treated with hydroxyurea or leukapheresis.
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
Targeted therapy
- Venetoclax (Venclexta) as follows:
- Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28
- Cycle 2 onwards: 400 mg PO once per day
28-day cycles
References
- M14-358: DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. link to original article contains dosing details in manuscript PubMed NCT02203773
- Update: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. link to original article link to PMC article PubMed
- VIALE-A: DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. link to original article contains dosing details in abstract PubMed NCT02993523
- ENHANCE-2: NCT04778397
Azacitidine & Gemtuzumab ozogamicin
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Nand et al. 2008 | NR in abstract | Phase 2 |
Nand et al. 2013 (SWOG S0703) | 2008-NR | Phase 2 |
Note: Patients with WBC greater than 10 x 109/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 109/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.
Supportive therapy, pre-treatment phase
- Hydroxyurea (Hydrea) 1500 mg PO twice per day or in higher doses if necessary
Once WBC is less than 10 x 109/L, stop Hydrea and proceed:
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 8
Supportive therapy
- "Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)
8-day course
Subsequent treatment
- If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered
- Patients achieving CR or CRi: Azacitidine and gemtuzumab ozogamicin consolidation, within 60 days
References
- Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. link to original article contains dosing details in manuscript PubMed
- SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814
Clofarabine monotherapy
Regimen variant #1, 20 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2012 (UK NCRI AML16) | 2006-2010 | Phase 3 (E-switch-ic) | LoDAC | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2013 update.
Chemotherapy
- Clofarabine (Clolar) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
4- to 6-week cycle for 4 cycles
Regimen variant #2, 30 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2010 (UWCM-001) | 2003-2005 | Phase 2 | ||
Faderl et al. 2008 (MDACC 2004-0183) | 2004-NR | Randomized Phase 2 (E-de-esc) | Clofarabine & LoDAC | Seems to have inferior EFS |
Burnett et al. 2010 (BIOV-121) | 2004-2005 | Phase 2 |
Chemotherapy
- Clofarabine (Clolar) 30 mg/m2 IV over 60 minutes once per day on days 1 to 5
5-day course
Subsequent treatment
- A second induction was permitted for SD or better.
- MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation
References
- MDACC 2004-0183: Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00088218
- UWCM-001; BIOV-121: Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. link to original article PubMed
- UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
- Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
- Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
Clofarabine & LoDAC
Clofarabine & LoDAC: Clofarabine & Low Dose Ara-C (Cytarabine)
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faderl et al. 2008 (MDACC 2004-0183) | 2004-NR | Randomized Phase 2 (E-esc) | Clofarabine | Seems to have superior EFS |
Chemotherapy
- Clofarabine (Clolar) 30 mg/m2 IV over 60 minutes once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 20 mg SC once per day on days 1 to 14, given 4 hours after clofarabine on days 1 to 5
28- to 49-day cycle for up to 2 cycles
Subsequent treatment
- CRi or better: Clofarabine & LoDAC consolidation
Regimen variant #2
Study | Years of enrollment | Evidence |
---|---|---|
Faderl et al. 2010 | 2008-2010 | Phase 2 |
Chemotherapy
- Clofarabine (Clolar) 20 mg/m2 IV once per day on days 1 to 5
- Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10
10-day course
Subsequent treatment
- Patients not achieving CR: Optional identical Clofarabine & LoDAC re-induction after at least 28 days
- Patients not achieving CR after the second induction: Decitabine salvage
- Patients achieving CR: Clofarabine & low-dose cytarabine alternating with decitabine consolidation
References
- MDACC 2004-0183: Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00088218
- Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. link to original article link to PMC article PubMed
- Update: Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. link to original article link to PMC article PubMed
CPX-351 monotherapy
CPX-351: Liposomal Cytarabine and Daunorubicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lancet et al. 2014 (CLTR0308-204) | 2008-2009 | Randomized Phase 2 (E-switch-ic) | 7+3d; intermediate-dose | Might have superior ORR |
Lancet et al. 2018 (CLTR0310-301) | 2012-2014 | Phase 3 (E-RT-switch-ic) | 7+3d; intermediate-dose | Superior OS1 Median OS: 9.3 vs 6.0 mo (HR 0.70, 95% CI 0.55-0.91) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- CPX-351 (Vyxeos) as follows:
- First induction: 100 units/m2 IV over 90 minutes once per day on days 1, 3, 5
- Second induction (if needed): 100 units/m2 IV over 90 minutes once per day on days 1 & 3
One or two courses
Subsequent treatment
- CR/CRi: CPX-351 consolidation
References
- CLTR0308-204: Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. link to original article link to PMC article PubMed NCT00788892
- CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
- Update: Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. link to original article PubMed
Decitabine monotherapy
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Issa et al. 2014 | NR | Randomized Phase 2 (C) | Decitabine & Valproate | Did not meet primary endpoint |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
4- to 6-week cycles
Regimen variant #2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kantarjian et al. 2012 (DACO-016) | 2006-2009 | Phase 3 (E-esc) | 1. LoDAC 2. Best supportive care |
Might have superior OS Median OS: 7.7 vs 5 mo (HR 0.85, 95% CI 0.69-1.04) |
Kantarjian et al. 2021 (SEAMLESS) | 2011-2014 | Phase 3 (C) | Decitabine/Sapacitabine | Did not meet primary endpoint of OS |
Montesinos et al. 2020 (JNJ AML2002) | 2015-2018 | Phase 2/3 (C) | Decitabine & Talacotuzumab | Did not meet primary endpoints of CR/OS |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
Supportive therapy
- Hydroxyurea (Hydrea) (dose not specified) could be used up until cycle 1 day 15
28-day cycles
Regimen variant #3
Study | Years of enrollment | Evidence |
---|---|---|
Blum et al. 2010 (OSU 07017) | 2007-NR | Phase 2 |
Welch et al. 2016 (Wash U 201210102) | 2013-2015 | Phase 2 |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 10
Supportive therapy
- Hydroxyurea (Hydrea) (dose not specified) allowed during and prior to cycle 1
28-day cycles
Subsequent treatment
- OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above
- OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by decitabine maintenance
References
- OSU 07017: Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00492401
- DACO-016: Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00260832
- Subgroup analysis: Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. link to original article PubMed
- Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015 Feb 15;121(4):556-61. Epub 2014 Oct 21. link to original article contains dosing details in manuscript link to PMC article PubMed
- Wash U 201210102: Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon D, Lee Y, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01687400
- JNJ AML-2002: Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02472145
- SEAMLESS: Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. link to original article contains dosing details in abstract PubMed NCT01303796
Decitabine & Venetoclax
Regimen variant #1, 5 days of decitabine
Study | Years of enrollment | Evidence |
---|---|---|
DiNardo et al. 2018 (M14-358) | 2014-2015 | Phase 1b, >20 pts (RT) |
Note: Patients with WBC greater than 25 x 109/L at presentation were pre-treated with hydroxyurea or leukapheresis.
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV or SC once per day on days 1 to 5
Targeted therapy
- Venetoclax (Venclexta) 400, 800, or 1200 mg PO once per day
28-day cycles
Regimen variant #2, 10 days of decitabine
Study | Years of enrollment | Evidence |
---|---|---|
DiNardo et al. 2020 (DEC10-VEN) | 2018-2019 | Phase 2 |
Note: Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m2 was allowed during cycle 1.
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV or SC once per day on days 1 to 10
Targeted therapy
- Venetoclax (Venclexta) as follows:
- Cycle 1: 400 mg PO once per day
- Cycle 2 onwards: 400 mg PO once per day on days 1 to 21
28-day cycles
References
- M14-358: DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. link to original article contains dosing details in manuscript PubMed NCT02203773
- Update: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. link to original article link to PMC article PubMed
- DEC10-VEN: DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. link to original article link to PMC article PubMed NCT03404193
Gemtuzumab ozogamicin monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Amadori et al. 2016 (EORTC/GIMEMA AML-19) | 2004-2013 | Phase 3 (E-RT-esc) | Best supportive care | Superior OS Median OS: 4.9 vs 3.6 mo (HR 0.69, 95% CI 0.53-0.90) |
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 6 mg/m2 IV once on day 1, then 3 mg/m2 IV once on day 8
8-day course
Subsequent treatment
- Patients with benefit: Gemtuzumab ozogamicin maintenance
References
- EORTC/GIMEMA AML-19: Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. link to original article contains dosing details in manuscript PubMed NCT00091234
Glasdegib & LoDAC
Glasdegib & LoDAC: Glasdegib & Low Dose Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2018 (BRIGHT AML 1003) | 2014-NR | Randomized Phase 2 (E-RT-esc) | LoDAC | Superior OS1 Median OS: 8.3 vs 4.3 mo (HR 0.495, 95% CI 0.325-0.75) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10
Targeted therapy
- Glasdegib (Daurismo) 100 mg PO once per day
28-day cycles
References
- BRIGHT AML 1003: Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. link to original article link to PMC article PubMed NCT01546038
- Update: Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. link to original article link to PMC article PubMed
Low-dose Cytarabine monotherapy (LoDAC)
LoDAC: Low Dose Ara-C (Cytarabine)
LDAC: Low-dose Ara-C (Cytarabine)
Regimen variant #1, 20 mg twice per day, indefinite duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kantarjian et al. 2013 (SPARK-AML1) | 2009-2010 | Randomized Phase 2 (C) | Barasertib & LoDAC | Seems to have inferior OCRR |
Döhner et al. 2014 (BI 1230.4) | 2010-2011 | Randomized Phase 2 (C) | LoDAC & Volasertib | Seems to have inferior OS |
Cortes et al. 2018 (BRIGHT AML 1003) | 2014-NR | Randomized Phase 2 (C) | Glasdegib & LoDAC | Inferior OS |
Regimen variant #2, 20 mg/m2 twice per day, limited duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burnett et al. 2012 (UK NCRI AML16) | 2006-2010 | Phase 3 (C) | Clofarabine | Did not meet primary endpoint of OS1 |
Sekeres et al. 2012 (SG033-0003) | 2007-2010 | Randomized Phase 2 (C) | LoDAC & Lintuzumab | Did not meet primary endpoint of OS |
Burnett et al. 2015 | 2010-2012 | Randomized (C) | Sapacitabine | Might have inferior CR rate |
Dombret et al. 2015 (AZA-AML-001) | 2010-2014 | Phase 3 (C) | Azacitidine | Might have inferior OS |
Dennis et al. 2015 (UK NCRI LI-1) | 2012-2013 | Randomized (C) | 1. LDAC & Vosaroxin | Did not meet primary endpoint of CR/CRi rate |
2. Vosaroxin | Did not meet primary endpoint of CR/CRi rate |
1Reported efficacy for UK NCRI AML16 is based on the 2016 update.
Chemotherapy
- Cytarabine (Ara-C) 20 mg/m2 SC twice per day on days 1 to 10
4- to 6-week cycle for up to 4 cycles
Regimen variant #3, 20 mg/m2 once per day, indefinite duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kantarjian et al. 2012 (DACO-016) | 2006-2009 | Phase 3 (C) | Decitabine | Might have inferior OS |
Wei et al. 2020 (VIALE-C) | 2017-2018 | Phase 3 (C) | LoDAC & Venetoclax | Seems to have inferior OS1 |
1Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.
References
- DACO-016: Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00260832
- Subgroup analysis: Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. link to original article PubMed
- SG033-0003: Sekeres MA, Lancet JE, Wood BL, Grove LE, Sandalic L, Sievers EL, Jurcic JG. Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica. 2013 Jan;98(1):119-28. Epub 2012 Jul 16. link to original article link to PMC article PubMed NCT00528333
- UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
- Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
- Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
- SPARK-AML1: Kantarjian HM, Martinelli G, Jabbour EJ, Quintás-Cardama A, Ando K, Bay JO, Wei A, Gröpper S, Papayannidis C, Owen K, Pike L, Schmitt N, Stockman PK, Giagounidis A; SPARK-AML1 Investigators. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013 Jul 15;119(14):2611-9. Epub 2013 Apr 19. link to original article link to PMC article contains dosing details in abstract PubMed NCT00952588
- BI 1230.4: Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Müller-Tidow C, Krämer A, Raffoux E, Döhner K, Schlenk RF, Voss F, Taube T, Fritsch H, Maertens J. Randomized, phase 2 trial comparing low-dose cytarabine with or without volasertib in AML patients not suitable for intensive induction therapy. Blood. 2014 Aug 28;124(9):1426-33. Epub 2014 Jul 8. link to original article link to PMC article PubMed NCT00804856
- Burnett AK, Russell N, Hills RK, Panoskaltsis N, Khwaja A, Hemmaway C, Cahalin P, Clark RE, Milligan D. A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia. Leukemia. 2015 Jun;29(6):1312-9. Epub 2015 Feb 13. link to original article contains dosing details in manuscript PubMed
- UK NCRI LI-1: Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood. 2015 May 7;125(19):2923-32. Epub 2015 Mar 24. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN40571019
- AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01074047
- Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
- BRIGHT AML 1003: Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. link to original article link to PMC article PubMed NCT01546038
- Update: Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. link to original article link to PMC article PubMed
- VIALE-C: Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03069352
- Update: Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. link to original article link to PMC article PubMed
- POLO-AML-2: NCT01721876
LoDAC & Venetoclax
LoDAC & Venetoclax: Low Dose Ara-C (Cytarabine) & Venetoclax
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wei et. al. 2019 (M14-387) | 2015-2017 | Phase 1b/2 (RT) | ||
Wei et al. 2020 (VIALE-C) | 2017-2018 | Phase 3 (E-RT-esc) | LoDAC | Seems to have superior OS1 Median OS: 8.4 vs 4.1 mo (HR 0.70, 95% CI 0.50-0.99) |
1Reported efficacy for VIALE-C is based on the 2021 update.
Chemotherapy
- Cytarabine (Ara-C) 20 mg/m2 SC once per day on days 1 to 10
Targeted therapy
- Venetoclax (Venclexta) as follows:
- Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28
- Cycle 2 onwards: 600 mg PO once per day
28-day cycles
Dose modifications
- M14-387: The dose of venetoclax was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors.
References
- M14-387: Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02287233
- VIALE-C: Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03069352
- Update: Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. link to original article link to PMC article PubMed
Temozolomide monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Brandwein et al. 2014 | NR | Phase 2 |
Note: Patient selection was based on MGMT expression by Western blot. See article for details.
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2/day PO on days 1 to 7
- Complete responders could receive: 200 mg/m2/day PO on days 1 to 5
28-day cycle for up to 12 cycles
References
- Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. link to original article contains dosing details in abstract PubMed
Consolidation after upfront therapy
5+2d
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Lancet et al. 2018 (CLTR0310-301) | 2012-2014 | Non-randomized portion of phase 3 RCT |
Preceding treatment
- 7+3d; intermediate-dose
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 & 2
5-day course
References
- CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
High-dose Cytarabine monotherapy (HiDAC)
HiDAC: High Dose Ara-C (Cytarabine)
HDAC: High Dose Ara-C (Cytarabine)
HDAraC: High Dose AraC (Cytarabine)
Regimen variant #1, 2000 mg/m2 every 12 hours x 6
Study | Years of enrollment | Evidence |
---|---|---|
Holowiecki et al. 2012 (PALG AML1/2004) | 2004-2008 | Non-randomized portion of phase 3 RCT |
Details in the text are scant.
Preceding treatment
- Cytarabine & Mitoxantrone consolidation
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m2)
5-day course
Regimen variant #2, 2 cycles of 2000 mg/m2 every 12 hours x 10
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Fukushima et al. 2012 | 2002-2006 | Randomized, <20 pts in this arm (C) | mIDAC | Seems to be more toxic |
Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m2)
28-day cycle for 2 cycles
Subsequent treatment
- A-VVV
Regimen variant #3, 1 cycle of 3000 mg/m2 every 12 hours x 12
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cassileth et al. 1998 | 1990-1995 | Phase 3 (C) | BuCy, then auto HSCT | Seems to have superior OS |
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m2)
6-day course
Regimen variant #4, 3 cycles of 3000 mg/m2 every 12 hours x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moore et al. 2004 (CALGB 9222) | 1992-1995 | Phase 3 (C) | HiDAC, then CYVE, then AZQ & Mitoxantrone | Did not meet primary endpoint of DFS |
Schaich et al. 2013 (AML2003) | 2003-2009 | Phase 3 (C) | MAC/MAMAC/MAC | Did not meet primary endpoint of DFS |
Petersdorf et al. 2013 (SWOG S0106) | 2004-2009 | Non-randomized portion of phase 3 RCT | ||
Stone et al. 2015 (ACCEDE) | 2008-2010 | Non-randomized portion of phase 3 RCT | ||
Röllig et al. 2015 (SORAML) | 2009-2011 | Randomized Phase 2 (C) | HiDAC & Sorafenib | Seems to have inferior EFS |
Stone et al. 2015 (COSAH C-022) | 2010-2014 | Non-randomized portion of phase 3 RCT |
Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.
Preceding treatment
- CALGB 9222: 7+3d; standard-dose
- SWOG S0106: 7+3d; intermediate-dose versus 7+3d & GO
- AML2003: 7+3d; intermediate-dose x 2
- ACCEDE: Amonafide & Cytarabine versus 7+3d; standard-dose
- SORAML: 7+3d; intermediate-dose versus 7+3d & Sorafenib
- COSAH C-022: 7+3d; high-dose versus 7+3i
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m2)
3 cycles of varying durations
Subsequent treatment
- SWOG S0106: GO maintenance versus no further treatment
Regimen variant #5, 3 cycles of 2000 mg/m2 every 12 hours x 10
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ohtake et al. 2010 (JALSG AML201) | 2001-2005 | Phase 3 (E-de-esc) | Multiagent chemotherapy | Did not meet primary endpoint of DFS |
Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m2)
3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 109/L, and 100 × 109/L
Regimen variant #6, 4 cycles of 3000 mg/m2 every 12 hours x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mayer et al. 1994 (CALGB 8525) | 1985-1990 | Phase 3 (E-esc) | Low-dose continuous infusion cytarabine | Seems to have superior OS |
Thomas et al. 2011 (ALFA-9802) | 1999-2006 | Phase 3 (C) | Timed sequential chemotherapy (TSC) | Did not meet primary endpoint of EFS |
Lee et al. 2017 (COSAH C-022) | 2010-2014 | Non-randomized portion of phase 3 RCT |
Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m2)
28-day cycle for up to 4 cycles
Subsequent treatment
- ALFA-9802: Cytarabine & Daunorubicin maintenance
References
- CALGB 8525: Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; CALGB. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. link to original article contains dosing details in manuscript PubMed
- Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. link to original article contains dosing details in manuscript PubMed
- CALGB 9222: Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. link to original article link to PMC article contains dosing details in manuscript PubMed
- JALSG AML201: Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, Okumura H, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2358-65. Epub 2010 Aug 6. link to original article PubMed C000000157
- Update: Miyawaki S, Ohtake S, Fujisawa S, Kiyoi H, Shinagawa K, Usui N, Sakura T, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2366-72. Epub 2010 Dec 29. link to original article contains dosing details in manuscript PubMed
- ALFA-9802: Thomas X, Elhamri M, Raffoux E, Renneville A, Pautas C, de Botton S, de Revel T, Reman O, Terré C, Gardin C, Chelghoum Y, Boissel N, Quesnel B, Hicheri Y, Bourhis JH, Fenaux P, Preudhomme C, Michallet M, Castaigne S, Dombret H. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study. Blood. 2011 Aug 18;118(7):1754-62. Epub 2011 Jun 20. link to original article contains dosing details in manuscript PubMed NCT00880243
- Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains dosing details in manuscript PubMed
- SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article PubMed NCT00085709
- AML2003: Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. link to original article contains dosing details in manuscript PubMed NCT00180102
- ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637
- PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
- SORAML: Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. link to original article contains dosing details in abstract PubMed NCT00893373
- COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846
Intermediate-dose Cytarabine monotherapy (IDAC)
IDAC: Intermediate Dose Ara-C (Cytarabine)
mIDAC: modified Intermediate Dose Ara-C (Cytarabine)
Regimen variant #1, 1000 mg/m2 x 3
Study | Years of enrollment | Evidence |
---|---|---|
Stone et al. 2015 (ACCEDE) | 2008-2010 | Non-randomized portion of phase 3 RCT |
Preceding treatment
- Amonafide & Cytarabine versus 7+3d; standard-dose
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m2)
3 cycles (length not specified)
Regimen variant #2, 1000 mg/m2 x 10
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Fukushima et al. 2012 | 2002-2006 | Randomized, <20 pts in this arm (E-de-esc) | HDAC | Seems to be less toxic |
Note: cycle length was not specified; 28-day cycles are frequently used in this setting.
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m2)
28-day cycle for 2 cycles (see note)
Subsequent treatment
- A-VVV
Regimen variant #3, 1000 mg/m2 x 12
Study | Years of enrollment | Evidence |
---|---|---|
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | 2000-2006 | Non-randomized portion of phase 3 RCT |
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m2)
6-day course
Subsequent treatment
- Transplant eligible patients: allogeneic HSCT
- Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus no further treatment
References
- HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
- Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains dosing details in manuscript PubMed
- ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637
HiDAC & G-CSF
HiDAC & G-CSF: High Dose Ara-C (Cytarabine) & Granulocyte Colony Stimulating Factor
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thomas et al. 2017 (ALFA-0702) | 2009-2013 | Randomized Phase 2 (C) | CLARA | Seems to have inferior RFS |
Preceding treatment
- Cytarabine, Daunorubicin, G-CSF induction
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m2)
Growth factor therapy
- Filgrastim (Neupogen) 5 mcg/kg IV once per day on days 1 to 5
35-day cycle for 3 cycles
References
- ALFA-0702: Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. link to original article contains dosing details in supplement PubMed NCT00932412
Azacitidine monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Nand et al. 2013 (SWOG S0703) | 2008-NR | Phase 2 |
Preceding treatment
- Azacitidine & Gemtuzumab ozogamicin consolidation
References
- SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814
Azacitidine & Gemtuzumab ozogamicin
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Nand et al. 2013 (SWOG S0703) | 2008-NR | Phase 2 |
Preceding treatment
- Azacitidine & Gemtuzumab ozogamicin induction
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 8
Supportive therapy
- "Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)
- Growth factors per physician discretion
8-day course
Subsequent treatment
- Azacitidine maintenance, within 42 days of completion of consolidation
References
- SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814
BuCy, then auto HSCT
BuCy: Busulfan & Cyclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | 1995-2006 | Phase 3 (E-esc) | Etoposide & Mitoxantrone | Might have superior RFS |
Preceding treatment
- 7+3i, then Amsacrine & Cytarabine
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO (frequency not specified) on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- HOVON-SAKK AML-29/AML-42: Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains dosing details in manuscript PubMed
BuFlu, then allo HSCT
BuFlu: Busulfan & Fludarabine
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Devine et al. 2015 (CALGB 100103) | 2004-2011 | Phase 2, <20 pts in subgroup |
Nand et al. 2013 (SWOG S0703) | 2008-NR | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -7 to -3
- MC-FludT.14/L gave the doses on days -6 to -2
- Busulfan (Myleran) 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- ATG (Rabbit) 2.5 mg/kg IV over 6 hours once per day on days -4 to -2
- Tacrolimus (Prograf) with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD)
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6, +11
One course
References
- CALGB 100103: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00070135
CIA
CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Nazha et al. 2013 | 2010-2012 | Phase 2 |
Preceding treatment
- CIA induction
Chemotherapy
- Clofarabine (Clolar) 15 mg/m2 IV once per day on days 1 to 3
- Idarubicin (Idamycin) 8 mg/m2 IV once per day on days 1 & 2
- Cytarabine (Ara-C) 750 mg/m2 IV once per day on days 1 to 3
21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity
References
- Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. long link to original article contains dosing details in manuscript link to PMC article PubMed
CLARA
CLARA: CLofarabine and ARA-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thomas et al. 2017 (ALFA-0702) | 2009-2013 | Randomized Phase 2 (E-esc) | HiDAC & G-CSF | Seems to have superior RFS |
Preceding treatment
- Cytarabine, Daunorubicin, G-CSF induction
Chemotherapy
- Clofarabine (Clolar) 30 mg/m2 IV over 2 hours once per day on days 2 to 6, given first
- Cytarabine (Ara-C) 1000 mg/m2 IV over 2 hours once per day on days 1 to 5, given second, 4 hours after clofarabine, on days 2 to 5
Growth factor therapy
- Filgrastim (Neupogen) 5 mcg/kg IV once per day on days 1 to 6
35-day cycle for 3 cycles
References
- ALFA-0702: Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. link to original article contains dosing details in supplement PubMed NCT00932412
Clofarabine & LoDAC/Decitabine
Clofarabine & LoDAC/Decitabine: Clofarabine & Low Dose Ara-C (Cytarabine) alternating with Decitabine
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Faderl et al. 2010 | 2008-2010 | Phase 2 |
Preceding treatment
- Clofarabine & LoDAC, which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities.
Chemotherapy, clofarabine & LoDAC portion
- Clofarabine (Clolar) as follows:
- Cycles 2, 3, 7 to 9, 13 to 15: 20 mg/m2 IV once per day on days 1 to 3
- Cytarabine (Ara-C) as follows:
- Cycles 2, 3, 7 to 9, 13 to 15: 20 mg SC twice per day on days 1 to 7
4- to 7-week cycles, depending on count recovery
Chemotherapy, decitabine portion
- Decitabine (Dacogen) as follows:
- Cycles 4 to 6, 10 to 12, 16 to 18: 20 mg/m2 IV once per day on days 1 to 5
4- to 7-week cycles, depending on count recovery
References
- Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. link to original article contains dosing details in manuscript link to PMC article PubMed
- Update: Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. link to original article link to PMC article PubMed
CPX-351 monotherapy
CPX-351: Liposomal Cytarabine and Daunorubicin
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Lancet et al. 2018 (CLTR0310-301) | 2012-2014 | Non-randomized portion of phase 3 RCT |
Preceding treatment
- CPX-351 induction
Chemotherapy
- CPX-351 (Vyxeos) 65 units/m2 IV over 90 minutes once per day on days 1 & 3
5- to 8-week cycle for 2 cycles
References
- CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
Cytarabine & Daunorubicin
Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Castaigne et al. 2012 (ALFA-0701) | 2008-2010 | Non-randomized portion of phase 3 RCT |
Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 109 at day 45 from initiation of chemotherapy were assigned to this regimen.
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m2)
- Daunorubicin (Cerubidine) as follows:
- Cycle 1: 60 mg/m2 IV once on day 1
- Cycle 2: 60 mg/m2 IV once per day on days 1 & 2
2 cycles (length not specified)
Regimen variant #2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gardin et al. 2007 (ALFA 9803) | 1999-2006 | Phase 3 (E-esc) | 4d + 7 | Seems to have superior OS |
Preceding treatment
- 4d + 7 induction
Chemotherapy
- Cytarabine (Ara-C) 60 mg/m2 SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m2)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once on day 1
1-month cycle for up to 6 cycles
References
- ALFA 9803: Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. link to original article contains dosing details in manuscript PubMed NCT00363025
- ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
- Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
Cytarabine, Daunorubicin, Gemtuzumab ozogamicin
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Castaigne et al. 2012 (ALFA-0701) | 2008-2010 | Non-randomized portion of phase 3 RCT |
Preceding treatment
- 7+3d & GO induction
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m2)
- Daunorubicin (Cerubidine) as follows:
- Cycle 1: 60 mg/m2 IV once on day 1
- Cycle 2: 60 mg/m2 IV once per day on days 1 & 2
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 (maximum dose of 5 mg) IV once on day 1
2 cycles (length not specified)
References
- ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
- Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
CYVE
CYVE: CYtarabine & VEpesid (Etoposide)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Lee et al. 2017 (COSAH C-022) | 2010-2014 | Non-randomized portion of phase 3 RCT |
Note: this consolidation regimen was for patients with high-risk cytogenetics.
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV once per day on days 1 to 6
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 to 3
4 courses
Subsequent treatment
- Transplant eligible patients with available donors usually proceeded to allogeneic HSCT after 2 courses (details not specified)
References
- COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846
Cytarabine & Idarubicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gardin et al. 2007 (ALFA 9803) | 1999-2006 | Phase 3 (E-esc) | 4i + 7 | Seems to have superior OS |
Preceding treatment
- 4i + 7 induction
Chemotherapy
- Cytarabine (Ara-C) 60 mg/m2 SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m2)
- Idarubicin (Idamycin) 9 mg/m2 IV once on day 1
1-month cycle for up to 6 cycles
References
- ALFA 9803: Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. link to original article contains dosing details in manuscript PubMed NCT00363025
Cytarabine, Idarubicin, Sorafenib
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Ravandi et al. 2010 (BAY43-9006) | 2007-2009 | Phase 1/2 |
Regimen details are from the phase 2 part of the published phase 1/2 trial.
Preceding treatment
- 7+3i & Sorafenib induction
Chemotherapy
- Cytarabine (Ara-C) 750 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 2250 mg/m2)
- Idarubicin (Idamycin) 8 mg/m2 IV over 60 minutes once per day on days 1 & 2
Targeted therapy
- Sorafenib (Nexavar) 400 mg PO twice per day for up to 28 days
4- to 6-week cycle for up to 5 cycles
Subsequent treatment
- Sorafenib maintenance
References
- BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
- Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed
Cyclophosphamide & TBI, then allo HSCT
Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Blume et al. 1980 | 1976-1979 | Non-randomized, <20 pts | |||
Zittoun et al. 1995 | 1986-1993 | Phase 3 (E-esc) | Intensive chemotherapy | Superior DFS | |
Bornhäuser et al. 2012 (9005-2003) | 2004-2009 | Phase 3 (C) | Fludarabine & TBI, then allo HSCT | Did not meet secondary efficacy endpoints | Did not meet primary endpoint of NRM |
Preceding treatment
- Zittoun et al. 1995: 7+3d with CR, then Amsacrine & IDAC
Details in most of the manuscripts are limited.
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation by the following study-specific criteria:
- Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
- Other studies: 10 to 1200 cGy total
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. link to original article PubMed
- Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; EORTC; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. link to original article contains dosing details in abstract PubMed
- 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in abstract PubMed NCT00150878
- Retrospective: Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. link to original article link to PMC article PubMed
Etoposide & Mitoxantrone
ME: Mitoxantrone & Etoposide
Regimen variant #1, 3 days
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (AMLSG31-19) | 2021-ongoing | Phase 3 (C) | ME & Venetoclax | In progress |
Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.
Preceding treatment
- 7+3d induction
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 to 3
One course
Regimen variant #2, 5 days
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | 1995-2006 | Phase 3 (C) | Bu/Cy, then auto HSCT | Might have inferior RFS |
Preceding treatment
- 7+3i, then Amsacrine & Cytarabine
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 to 5
One course
References
- HOVON-SAKK AML-29/AML-42: Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains dosing details in manuscript PubMed
- AMLSG31-19: NCT04628026
Fludarabine & TBI, then allo HSCT
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Bornhäuser et al. 2012 (9005-2003) | 2004-2009 | Phase 3 (E-switch-ic) | Cyclophosphamide & TBI, then allo HSCT | Did not meet secondary efficacy endpoints | Did not meet primary endpoint of NRM |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -3
Radiotherapy
- Total body irradiation (TBI) 200 cGy fractions x 4 doses on days -3 & -2 (800 cGy total)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Immunotherapy
Stem cells transfused on day 0
Regimen variant #2, low-dose TBI
Study | Years of enrollment | Evidence |
---|---|---|
Gyukocza et al. 2010 | 1998-2008 | Non-randomized |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -4 to -2
Radiotherapy
- Total body irradiation (TBI) 200 cGy at a rate of 7 cGy/min on day 0
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD)
- Mycophenolate mofetil (CellCept) 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD)
One course
Immunotherapy
Stem cells transfused on day 0
References
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains dosing details in manuscript link to PMC article PubMed
- 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in abstract PubMed NCT00150878
Fludarabine, Busulfan, ATG, then allo HSCT
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Devine et al. 2015 (CALGB 100103) | 2004-2011 | Phase 2 |
Immunotherapy
Stem cells transfused on day 0
References
- CALGB 100103: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00070135
HAM
HAM: High-dose Ara-C (Cytarabine), Mitoxantrone
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Wierzbowksa et al. 2007 | NR in abstract | Phase 2 |
Holowiecki et al. 2012 (PALG AML1/2004) | 2004-2008 | Non-randomized portion of phase 3 RCT |
Chemotherapy
- Cytarabine (Ara-C) 1500 mg/m2 IV once per day on days 1 to 3
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 3 to 5
Subsequent treatment
- HiDAC consolidation
References
- Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
- PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
IC & Norethandrolone/6-MP, MTX, Norethandrolone
IC & Norethandrolone: Idarubicin, Cytarabine, Norethandrolone
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pigneux et al. 2016 (GOELAMS LAM-SA2002) | 2002-2005 | Phase 3 (E-esc) | IC/6-MP & MTX | Superior OS |
Preceding treatment
Chemotherapy, reinduction
- Idarubicin (Idamycin) 8 mg/m2 IV once on day 1
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m2)
Endocrince therapy, reinduction
- Norethandrolone (Nilevar) by the following weight-based criteria:
- If less than 60 kg: 10 mg PO once per day
- If greater than 60 kg: 20 mg PO once per day
3-month cycle for 6 cycles, alternating with maintenance
Chemotherapy, maintenance
- Methotrexate (MTX) by the following weight-based criteria:
- If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11
- If greater than 60 kg: 25 mg PO once per day on days 1, 4, 8, 11
- Mercaptopurine (6-MP) by the following weight-based criteria:
- If less than 60 kg: 100 mg PO once per day on days 15 to 30
- If greater than 60 kg: 150 mg PO once per day on days 15 to 30
Endocrine therapy, maintenance
- Norethandrolone (Nilevar) by the following weight-based criteria:
- If less than 60 kg: 10 mg PO once per day
- If greater than 60 kg: 20 mg PO once per day
3-month cycle for 6 cycles, alternating with re-induction courses
References
- GOELAMS LAM-SA2002: Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. link to original article contains dosing details in manuscript PubMed NCT00700544
Low-dose TBI, then allo HSCT
TBI: Total Body Irradiation
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Gyukocza et al. 2010 | 1998-2008 | Non-randomized |
Radiotherapy
- Total body irradiation (TBI) 200 cGy at a rate of 0.07 to 0.2000 cGy/min on day 0
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- One of the following (further details not specified):
- Mycophenolate mofetil (CellCept)
One course
Immunotherapy
Stem cells transfused on day 0
References
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains dosing details in manuscript link to PMC article PubMed
Maintenance after first-line therapy
Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.
Azacitidine monotherapy
Regimen variant #1, 12 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Huls et al. 2019 (HOVON97) | 2009-2016 | Phase 3 (E-esc) | Observation | Superior DFS DFS12: 64% vs 42% (aHR 0.62, 95% CI 0.41-0.95) |
Preceding treatment
- At least 2 cycles of intensive chemotherapy
Chemotherapy
- Azacitidine (Vidaza) 50 mg/m2 SC once per day on days 1 to 5
28-day cycle for up to 12 cycles
Regimen variant #2, indefinite
Study | Years of enrollment | Evidence |
---|---|---|
Grövdal et al. 2010 | 2004-2006 | Phase 2 |
Intended to be used for transformed MDS patients in remission after AML induction therapy.
Preceding treatment
References
- Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. link to original article contains dosing details in manuscript PubMed
- HOVON97: Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. link to original article contains dosing details in abstract PubMed NTR1810
Decitabine monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Blum et al. 2010 (OSU 07017) | 2007-NR | Phase 2 |
Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.
Preceding treatment
- Decitabine induction
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC less than 500/uL) persisting greater than or equal to 14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle.
28-day cycles
References
- OSU 07017: Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00492401
Azacitidine oral monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wei et al. 2020 (QUAZAR AML-001) | 2013-2017 | Phase 3 (E-RT-esc) | Observation | Superior OS1 Median OS: 24.7 vs 14.8 mo |
1The proportional hazards assumption was violated, so hazard ratios are not reported.
Preceding treatment
References
- QUAZAR AML-001: Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. link to original article contains dosing details in abstract PubMed NCT01757535
Gemtuzumab ozogamicin monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Amadori et al. 2016 (EORTC/GIMEMA AML-19) | 2004-2013 | Non-randomized portion of phase 3 RCT |
Preceding treatment
- Gemtuzumab ozogamicin induction, with clinical benefit
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 2 mg/m2 IV once on day 1
1-month cycle for up to 8 cycles
References
- EORTC/GIMEMA AML-19: Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. link to original article contains dosing details in manuscript PubMed NCT00091234
Low-dose Cytarabine monotherapy (LoDAC)
LoDAC: Low Dose Ara-C (cytarabine)
LDAC: Low Dose Ara-C (cytarabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robles et al. 2000 (ECOG E5483) | 1984-1988 | Phase 3 (E-esc) | Observation | Might have superior DFS |
References
- ECOG E5483: Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. link to original article contains dosing details in abstract PubMed
Sorafenib monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Ravandi et al. 2010 (BAY43-9006) | 2007-2009 | Phase 1/2 |
Preceding treatment
- Cytarabine, Idarubicin, Sorafenib consolidation
Targeted therapy
- Sorafenib (Nexavar) 400 mg PO twice per day
Up to one year course, including consolidation
References
- BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
- Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed
Relapsed or refractory, salvage therapy
Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.
5+2d
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Zeidner et al. 2015 (JHOC-J1101) | 2011-2013 | Non-randomized portion of phase 2 RCT |
Preceding treatment
- 7+3d; high-dose
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m2)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 & 2
5-day course
References
- JHOC-J1101: Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01349972
ADE (standard-dose Ara-C)
ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Milligan et al. 2006 (MRC AML-HR) | 1998-2003 | Phase 3 (C) | FLA | Seems to have superior OS |
Chemotherapy
- Cytarabine (Ara-C) as follows:
- Course 1: 100 mg/m2 IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m2)
- Course 2: 100 mg/m2 IV push every 12 hours on days 1 to 8 (total dose: 1600 mg/m2)
- Daunorubicin (Cerubidine) 50 mg/m2 IV once per day on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
2 courses (length not specified)
References
- MRC AML-HR: Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. link to original article PubMed NCT00005863
CLAG
CLAG: CLadribine, Ara-C (Cytarabine), G-CSF
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Robak et al. 2000 | NR in abstract | Phase 2 |
Chemotherapy
- Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine
Growth factor therapy
- Filgrastim (Neupogen) 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine)
References
- Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. link to original article contains dosing details in manuscript PubMed
- Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed
CLAG-M
CLAG-M: CLadribine, Ara-C (Cytarabine), G-CSF, Mitoxantrone
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Wierzbowksa et al. 2007 | NR in abstract | Phase 2 |
Chemotherapy
- Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 to 3
Growth factor therapy
- Filgrastim (Neupogen) by the following criteria:
- WBC count less than or equal to 20 x 109/L: 300 mcg SC once per day on days 0 to 5, started 24 hours prior to chemotherapy
- WBC count greater than 20 x 109/L: 300 mcg SC once per day on days 1 to 5, started simultaneously to cladribine
6-day course
References
- Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
- Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed
CLARA
CLARA: CLofarabine and ARA-C (Cytarabine)
GCLAC: G-CSF, Clofarabine, Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Becker et al. 2011 (UW 6562) | 2007-NR | Phase 2 |
Chemotherapy
- Clofarabine (Clolar) 25 mg/m2 IV over 60 minutes once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 1 to 5, given second, 4 hours after start of clofarabine infusion
Growth factor therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days
6-day course
References
- UW 6562: Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00602225
Clofarabine & Cytarabine
Regimen variant #1, 20/20 variant 1
Study | Years of enrollment | Evidence |
---|---|---|
Buckley et al. 2015 (FHCRC 2302.00) | 2009-2013 | Phase 1/2 |
Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.
Chemotherapy
- Clofarabine (Clolar) 20 mg PO once per day on days 1 to 5
- Cytarabine (Ara-C) 20 mg/m2 SC twice per day on days 1 to 10
Cycle duration not explicitly defined; presumably 28 days
Regimen variant #2, 20/20 variant 2
Study | Years of enrollment | Evidence |
---|---|---|
Buckley et al. 2015 (FHCRC 2302.00) | 2009-2013 | Phase 1/2 |
Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.
Chemotherapy
- Clofarabine (Clolar) 20 mg PO once per day on days 1 to 5
- Cytarabine (Ara-C) 20 mg/m2 SC once per day on days 1 to 14
Cycle duration not explicitly defined; presumably 28 days
Regimen variant #3, 30/1000
Study | Years of enrollment | Evidence |
---|---|---|
Middeke et al. 2015 (BRIDGE) | 2012-2013 | Phase 2 |
Chemotherapy
- Clofarabine (Clolar) 30 mg/m2 IV once per day on days 1 to 5
- Cytarabine (Ara-C) 1000 mg/m2 IV once per day on days 1 to 5
At least one cycle
Subsequent treatment
- Chemo-responsive patients: Clofarabine & Melphalan, then allo HSCT
Regimen variant #4, 40/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faderl et al. 2004 | NR | Phase 1/2 | ||
Agura et al. 2011 (Baylor 004-145) | 2005-2006 | Phase 2 | ||
Faderl et al. 2012 (CLASSIC I) | 2006-2009 | Phase 3 (E-esc) | IDAC | Did not meet primary endpoint of OS |
Note: length of cycles was not specified; 28-day cycle is typical for this regimen.
Chemotherapy
- Clofarabine (Clolar) 40 mg/m2 IV over 60 minutes once per day on days 1 to 5, given first
- Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6
- Cytarabine (Ara-C) 1000 mg/m2 IV over 2 hours once per day on days 1 to 5, given second, 3 to 4 hours after completion of clofarabine infusion
Supportive therapy
- Best described in Agura et al. 2011
- Dexamethasone (Decadron) 10 mg IV once per day
- 5-HT3 antagonists on each day of chemotherapy
- Hydration at 150 mL/m2/H "to prevent tumor lysis syndrome" during chemotherapy
- Bumetanide (Bumex) 2 to 4 mg IV push once to twice per day as needed to keep weight within 1 kg of patient's initial weight
- Levofloxacin (Levaquin) 500 mg IV or PO once per day
- Acyclovir (Zovirax) 500 mg IV Q12H
- One of the following antifungals:
- Caspofungin (Cancidas) 50 mg IV once per day
- Voriconazole (Vfend) 200 mg (route not specified) twice per day
- Parenteral nutrition allowed
- No routine use of growth factors
28-day cycle for 1 to 4 cycles
Subsequent treatment
- See individual papers for details
References
- Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. link to original article contains dosing details in manuscript PubMed
- Baylor 004-145: Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00334074
- CLASSIC I: Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. Epub 2012 May 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00317642
- FHCRC 2302.00: Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. link to original article contains dosing details in manuscript PubMed
- BRIDGE: Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article contains dosing details in abstract PubMed
Etoposide & Mitoxantrone
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Ho et al. 1988 | 1984-1987 | Phase 2 | ORR: 54% |
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once per day on days 1 to 5
- Mitoxantrone (Novantrone) 10 mg/m2 IV over 15 minutes once per day on days 1 to 5
References
- Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. link to original article PubMed
FLAG
FLAG: FLudarabine, Ara-C (Cytarabine), G-CSF
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Montillo et al. 1998 | 1994-1996 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 1 to 5, given second, 4 hours after the start of fludarabine
Growth factor therapy
- G-CSF with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
- Lenograstim (Granocyte) 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
6-day course
References
- Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. link to original article contains dosing details in manuscript PubMed
FLAG-Ida
FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Filgrastim), Idarubicin
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Parker et al. 1997 | 1995-1997 | Phase 2, <20 patients |
Pastore et al. 2003 | 1998-2002 | Phase 2 |
Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 2000 mg/m2 IV over 4 hours once per day on days 1 to 5, given second, 4 hours after fludarabine
- Idarubicin (Idamycin) 10 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery
5-day course
References
- Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. link to original article PubMed
- Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. link to original article contains dosing details in abstract PubMed
F-SHAI
F-SHAI: Fludarabine, Sequential High-dose Ara-C (cytarabine), Idarubicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fiegl et al. 2013 | NR | Phase 3 (E-esc) | SHAI | Seems to have superior TTTF |
Chemotherapy
- Fludarabine (Fludara) 15 mg/m2 IV twice per day on days 1, 2, 8, 9, given 4 hours prior to each cytarabine dose
- Cytarabine (Ara-C) 1000 mg/m2 IV twice per day on days 1, 2, 8, 9
- Dose increased to 3000 mg/m2 for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
- Idarubicin (Idamycin) 10 mg/m2 IV once per day on days 3, 4, 10, 11
Supportive therapy
- G-CSF 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL
- Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts
11-day course
References
- Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. link to original article contains dosing details in manuscript PubMed
Gemtuzumab ozogamicin monotherapy
Regimen variant #1, fractionated dosing
Study | Years of enrollment | Evidence |
---|---|---|
Taksin et al. 2006 (MyloFrance-1) | 2005 | Phase 2 (RT) |
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once per day on days 1, 4, 7
One course
Regimen variant #2
Study | Years of enrollment | Evidence |
---|---|---|
Sievers et al. 2001 | 1997-1999 | Phase 2 (RT) |
Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.
Antibody-drug conjugate therapy
- Gemtuzumab ozogamicin (Mylotarg) 9 mg/m2 IV once on day 1
14-day cycle for 2 cycles
References
- Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. link to original article contains dosing details in abstract PubMed
- Update: Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, Mineur P, Bennett JM, Berger MS, Eten CB, Munteanu M, Loken MR, Van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia. 2002 Sep;16(9):1627-36. link to original article PubMed
- Update: Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. link to original article PubMed
- MyloFrance-1: Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. link to original article contains dosing details in manuscript PubMed
High-dose Cytarabine monotherapy (HiDAC)
HiDAC: High Dose Ara-C (Cytarabine)
Regimen variant #1, CI
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Giles et al. 2009 (VION-CLI-037) | 2005-2007 | Phase 3 (C) | HiDAC & Laromustine | Mixed response (see note) |
Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.
Chemotherapy
- Cytarabine (Ara-C) 1500 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m2)
3-day course
Regimen variant #2, intermittent
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Karanes et al. 1999 (SWOG-8326) | 1985-1992 | Phase 3 (C) | HiDAC & Mitoxantrone | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m2)
6-day course
References
- SWOG-8326: Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. link to original article contains dosing details in abstract PubMed
- VION-CLI-037: Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. link to original article contains dosing details in manuscript PubMed NCT00112554
MAC
MAC: Mitoxantrone & Ara-C (Cytarabine)
MIDAC: Mitoxantrone & Intermediate-Dose Ara-C (Cytarabine)
Regimen variant #1, 6000/25
Study | Years of enrollment | Evidence |
---|---|---|
Sternberg et al. 2000 | 1990-1997 | Phase 2 |
Chemotherapy
- Mitoxantrone (Novantrone) 5 mg/m2 IV bolus once per day on days 1 to 5
- Cytarabine (Ara-C) 500 mg/m2 IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m2)
6-day course
Regimen variant #2, 10,000/48
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Solary et al. 1996 | 1992-1995 | Phase 3 (C) | Cytarabine, Mitoxantrone, Quinine | Did not meet primary endpoint of CR rate |
Chemotherapy
- Mitoxantrone (Novantrone) 12 mg/m2 IV bolus once per day on days 2 to 5
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m2)
5-day course
References
- Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. link to original article contains dosing details in abstract PubMed
- Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. link to original article contains dosing details in manuscript PubMed
MEC
MEC: Mitoxantrone, Etoposide, Cytarabine
Regimen variant #1, 6/80/1000
Study | Years of enrollment | Evidence |
---|---|---|
Amadori et al. 1991 | 1988-1990 | Phase 2 |
Chemotherapy
- Mitoxantrone (Novantrone) 6 mg/m2 IV bolus once per day on days 1 to 6
- Etoposide (Vepesid) 80 mg/m2 IV over 60 minutes once per day on days 1 to 6
- Cytarabine (Ara-C) 1000 mg/m2 IV over 6 hours once per day on days 1 to 6
6-day course
Regimen variant #2, 8/80/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Feldman et al. 2005 | 1999-2001 | Phase 3 (C) | MEC & Lintuzumab | Did not meet primary endpoint of ORR |
Chemotherapy
- Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 to 6
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 6
- Cytarabine (Ara-C) 1000 mg/m2 IV once per day on days 1 to 6
6-day course
Regimen variant #3, 8/100/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Greenberg et al. 2004 (ECOG E2995) | NR-1999 | Phase 3 (C) | MEC & Valspodar | Did not meet primary endpoint of CR rate |
Cortes et al. 2014 (CLTR0308-205) | 2009-NR | Randomized Phase 2 (C) | CPX-351 | Did not meet primary endpoint of OS12 |
Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.
Chemotherapy
- Mitoxantrone (Novantrone) 8 mg/m2 IV push once per day on days 1 to 5, given third
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
- Cytarabine (Ara-C) 1000 mg/m2 IV once per day on days 1 to 5, given second
28-day cycle for 1 to 2 cycles
References
- Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. link to original article PubMed
- ECOG E2995: Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004 Jul 1;22(13):2747. link to original article link to PMC article contains dosing details in manuscript PubMed
- Feldman EJ, Brandwein J, Stone R, Kalaycio M, Moore J, O'Connor J, Wedel N, Roboz GJ, Miller C, Chopra R, Jurcic JC, Brown R, Ehmann WC, Schulman P, Frankel SR, De Angelo D, Scheinberg D. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005 Jun 20;23(18):4110-6. link to original article contains dosing details in manuscript PubMed
- CLTR0308-205: Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015 Jan 15;121(2):234-42. Epub 2014 Sep 15. link to original article link to PMC article PubMed NCT00822094
- D18-11141: NCT03926624
Consolidation after salvage therapy
BuCy, then allo HSCT
BuCy: Busulfan & Cyclophosphamide
Regimen variant #1, 12.8/120
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rambaldi et al. 2015 (GITMO-AMLR2) | 2008-2012 | Phase 3 (C) | BuFlu, then allo HSCT | Seems to have inferior 1-year non-relapse mortality |
Scott et al. 2017 (BMT CTN 0901) | 2011-2014 | Phase 3 (E-esc) | RIC allo HSCT | Might have superior OS |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg)
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine
- Methotrexate (MTX) "according to the discretion of the attending physician"
Supportive therapy
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL
One course
Immunotherapy
Stem cells transfused on day 0
Regimen variant #2, 16/200
Study | Years of enrollment | Evidence |
---|---|---|
Santos et al. 1983 | 1975-1982 | Non-randomized |
Note: the day of allogeneic stem cell transplant is not specified in the protocol.
Chemotherapy
- Busulfan (Myleran) 1 mg/kg IV every 6 hours on days 1 to 4 (total dose: 16 mg/kg)
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days 5 to 8 (total dose: 200 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on unspecified day
One course
Immunotherapy
Stem cells transfused on day 0
References
- Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. link to original article contains dosing details in abstract PubMed
- GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957
- BMT CTN 0901: Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. link to original article link to PMC article PubMed NCT01339910
BuFlu, then allo HSCT
BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rambaldi et al. 2015 (GITMO-AMLR2) | 2008-2012 | Phase 3 (E-switch-ic) | BuCy, then allo HSCT | Seems to improve 1 & 2 year NRM, similar OS |
Chemotherapy
- Busulfan (Myleran) 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -3
GVHD prophylaxis, pre-transplant
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Matched unrelated donors: 0.5 mg/kg IV once on day -3, then 2 mg/kg IV once on day -2, then 2.5 mg/kg IV once on day -1
- Mismatched donors: total ATG dose could be increased to 7.5 mg/kg
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis, post-transplant
One course
Immunotherapy
Stem cells transfused on day 0
Regimen variant #2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersson et al. 2008 | 1997-2005 | Non-randomized | Suggested improved outcomes, but shorter follow up |
Chemotherapy
- Busulfan (Myleran) 130 mg/m2 IV over 3 hours once per day on days -6 to -3
- Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels
- Fludarabine (Fludara) 40 mg/m2 IV over 60 minutes once per day on days -6 to -3, given first
GVHD prophylaxis, pre-transplant
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Unrelated or mismatched donors: 0.5 mg/kg IV once on day -3, then 1.5 mg/kg IV once on day -2, then 2 mg/kg IV once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis, post-transplant
#1 Tacrolimus & methotrexate based (Andersson et al.)
Supportive therapy
- All patients received Filgrastim (Neupogen) SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 x 109/L for three days
- Phenytoin (Dilantin) prophylaxis used during and for one day after IV busulfan
#2 Post-Transplant Cy based (Kanakry et al. and FHCC 2541.00)
GVHD prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts)
- ± Cyclosporine intravenous loading dose of CSP was given on day 5, followed by subsequent twice per day dosing adjusted to maintain whole blood trough at 120 to 360 ng/mL. In abscence of GVHD Cyclosporine was tapered from day +56 through day +126 (used in FHCC 2541.00 with PBSCT grafts)
Supportive therapy
- Mesna (Mesnex) given with cyclophosphamide
One course
Immunotherapy
Stem cells transfused on day 0
Regimen variant #3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2012 (COSAH C-005) | 2005-2009 | Phase 3 (E-switch-ic) | BuCy, then allo HSCT | Seems to have inferior OS |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4, given first on days overlapping with fludarabine (total dose: 12.8 mg/kg)
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2, given second on days overlapping with busulfan
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- "Cyclosporine
- Methotrexate (MTX) "according to the discretion of the attending physician"
Supportive therapy
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL
One course
Immunotherapy
Stem cells transfused on day 0
References
- Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. link to original article link to PMC article contains dosing details in manuscript Pubmed
- COSAH C-005: Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article contains dosing details in manuscript PubMed NCT00774280
- GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957
Clofarabine & Melphalan, then allo HSCT
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Middeke et al. 2015 (BRIDGE) | 2012-2013 | Phase 2 |
Limited details are available in the abstract. Treatment is meant to be given during aplasia.
Preceding treatment
- Clofarabine & Cytarabine salvage
Chemotherapy
- Clofarabine (Clolar) 4 x 30 mg/m2 IV
- Melphalan (Alkeran) 140 mg/m2 IV
Immunotherapy
- Allogeneic stem cells transfused on unspecified day
One course
References
- BRIDGE: Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article contains dosing details in abstract PubMed
Relapsed or refractory, subsequent lines of therapy
Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.
Azacitidine monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thepot et al. 2010 | 2004-2009 | Phase 2 | ||
Roboz et al. 2014 (CLAVELA) | 2010-2012 | Phase 3 (C) | Elacytarabine | Did not meet primary endpoint of OS |
Note: CLAVELA does not contain precise dosing information for the control arm regimens.
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 7
28-day cycle for at least 4 cycles
References
- Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. link to original article PubMed
- CLAVELA: Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. link to original article does not contain dosing details PubMed NCT01147939
Ruxolitinib monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Eghtedar et al. 2012 (MDACC 2007-0925) | 2008-2010 | Phase 2 |
Targeted therapy
- Ruxolitinib (Jakafi) 25 mg PO twice per day
- Patients with progression were allowed to increase the dose to 50 mg PO twice per day
28-day cycles
References
- MDACC 2007-0925: Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. link to original article contains dosing details in manuscript link to PMC article PubMed
Response criteria
NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)
- Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. link to original article PubMed
Revised International Working Group recommendations (2003)
- Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. link to original article PubMed
Prognosis
Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)
- Relapse-free interval from first complete remission
- Greater than 18 months (0 points)
- 7 to 18 months (3 points)
- Less than or equal to 6 months (5 points)
- Cytogenetics at diagnosis
- t(16;16) or inv(16) with or without additional cytogenetic abnormalities (0 points)
- t(8;21) with or without additional cytogenetic abnormalities (3 points)
- Normal, intermediate, unfavorable, or unknown cytogenetics (5 points)
- Age at time of first relapse
- Less than or equal to 35 years (0 points)
- 36 to 45 years (1 point)
- Greater than 45 years (2 points)
- Stem cell transplantation performed before first relapse
- No (0 points)
- Yes, autologous or allogeneic (2 points)
Risk stratification:
- 1 to 6 points: Favorable risk (1-year OS of 70%; 5-year OS of 46%)
- 7 to 9 points: Intermediate risk (1-year OS of 49%; 5-year OS of 18%)
- 10 to 14 points: Poor risk (1-year OS of 16%; 5-year OS of 4%)
References
- Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. link to original article PubMed
Prognosis in cytogenetically normal AML
- Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome: Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. link to original article PubMed
- CEBPA double mutations: Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. link to original article link to PMC article PubMed
Whole genome sequencing
- Seminal paper comparing WGS to cytogenetic analysis: Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. link to original article PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.
- Alvocidib (Flavopiridol)
- Pracinostat (SB939)
- Vadastuximab talirine (SGN-CD33A)
- Volasertib (BI 6727)
- Vosaroxin (SNS 595)