Difference between revisions of "Acute myeloid leukemia"
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==ELN== | ==ELN== | ||
====Current==== | ====Current==== | ||
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*'''2017:''' [http://www.bloodjournal.org/content/129/4/424.long Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27895058 PubMed] | *'''2017:''' [http://www.bloodjournal.org/content/129/4/424.long Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27895058 PubMed] | ||
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====Older==== | ====Older==== | ||
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*'''2010:''' [http://www.bloodjournal.org/content/115/3/453.long Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet] [https://www.ncbi.nlm.nih.gov/pubmed/19880497 PubMed] | *'''2010:''' [http://www.bloodjournal.org/content/115/3/453.long Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet] [https://www.ncbi.nlm.nih.gov/pubmed/19880497 PubMed] | ||
==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
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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] | ||
=="How I treat"== | =="How I treat"== | ||
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*'''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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524532/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27235136 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524532/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27235136 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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/25778528 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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''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.'' | ||
====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''' | ||
====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+3i | *ECOG E3993: Patients with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i | ||
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|} | |} | ||
====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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|} | |} | ||
====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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|} | |} | ||
====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''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
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*CALGB 9222: [[#HiDAC|HiDAC]] versus multi-agent chemotherapy consolidation | *CALGB 9222: [[#HiDAC|HiDAC]] versus multi-agent chemotherapy consolidation | ||
*HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]] | *HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]] | ||
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===References=== | ===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. [https://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6946847 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://www.ncbi.nlm.nih.gov/pubmed/4586956 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. [https://onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819820415%2949%3A8%3C1530%3A%3AAID-CNCR2820490804%3E3.0.CO%3B2-1 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7039813 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6946847 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. [http://www.bloodjournal.org/content/60/2/454.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6953986 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. [https://onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819820415%2949%3A8%3C1530%3A%3AAID-CNCR2820490804%3E3.0.CO%3B2-1 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7039813 PubMed] |
− | # Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L. A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial. Blood. 1984 May;63(5):1039-45. [http://www.bloodjournal.org/content/63/5/1039.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6201211 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. [http://www.bloodjournal.org/content/60/2/454.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6953986 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. [http://www.bloodjournal.org/content/69/5/1441.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3552076 PubMed] | + | #Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L. A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial. Blood. 1984 May;63(5):1039-45. [http://www.bloodjournal.org/content/63/5/1039.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6201211 PubMed] |
− | # Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A. 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. [https://www.sciencedirect.com/science/article/pii/014521269090179D link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/2259226 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. [http://www.bloodjournal.org/content/69/5/1441.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3552076 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. [http://www.bloodjournal.org/content/75/1/27.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2403818 PubMed] | + | #Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A. 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. [https://www.sciencedirect.com/science/article/pii/014521269090179D link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/2259226 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://www.ncbi.nlm.nih.gov/pubmed/2179638 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. [http://www.bloodjournal.org/content/75/1/27.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2403818 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. [http://www.bloodjournal.org/content/78/10/2520.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1824249 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://www.ncbi.nlm.nih.gov/pubmed/2179638 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 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. [http://www.bloodjournal.org/content/78/10/2520.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1824249 PubMed] |
− | # Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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. [http://ascopubs.org/doi/10.1200/JCO.1992.10.7.1103 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1607916 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 PubMed] | + | #Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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. [http://ascopubs.org/doi/10.1200/JCO.1992.10.7.1103 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1607916 PubMed] |
− | # Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. 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. [http://www.bloodjournal.org/content/88/8/2841.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8874180 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 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. [http://www.bloodjournal.org/content/100/12/3869.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12393614 PubMed] | + | #Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. 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. [http://www.bloodjournal.org/content/88/8/2841.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8874180 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 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. [http://www.bloodjournal.org/content/100/12/3869.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12393614 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. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 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. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2008.07400.x link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18950458 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. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2008.07400.x link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18950458 PubMed] |
− | # '''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 PubMed] |
− | ## '''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. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed] | + | #'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 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. [http://www.bloodjournal.org/content/118/14/3832.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21828126 PubMed] | + | ##'''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. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed] |
− | # '''AML 8B:''' 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. 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 Organization 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. [https://link.springer.com/article/10.1007%2Fs00277-012-1436-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345117/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22460947 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. [http://www.bloodjournal.org/content/118/14/3832.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21828126 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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed] | + | #'''AML 8B:''' 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. 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 Organization 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. [https://link.springer.com/article/10.1007%2Fs00277-012-1436-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345117/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22460947 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | ||
==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}== | ==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}== | ||
Line 328: | Line 341: | ||
''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.'' | ||
====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 | ||
Line 334: | Line 348: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*AML2003: [[#HiDAC|HiDAC]] versus MAC/MAMAC/MAC consolidation | *AML2003: [[#HiDAC|HiDAC]] versus MAC/MAMAC/MAC consolidation | ||
*SWOG S0106: [[#HiDAC|HiDAC consolidation]] x 3 | *SWOG S0106: [[#HiDAC|HiDAC consolidation]] x 3 | ||
Line 376: | Line 391: | ||
''Note: patients in RATIFY had FLT3+ disease.'' | ''Note: patients in RATIFY had FLT3+ disease.'' | ||
====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 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 | ||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*"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 | ||
Line 385: | Line 402: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====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|CLAG salvage]]. | + | *Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule. |
− | *Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#HiDAC|HiDAC]] consolidation | + | *PALG AML1/1999, non-responders: [[#CLAG|CLAG salvage]]. |
+ | *Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#HiDAC|HiDAC]] consolidation | ||
*ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin consolidation]] | *ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin consolidation]] | ||
===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 (PALG). 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://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20508614 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 (PALG). 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://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20508614 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 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://www.ncbi.nlm.nih.gov/pubmed/30076173 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 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://www.ncbi.nlm.nih.gov/pubmed/30076173 PubMed] |
− | # 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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4990 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23897964 PubMed] | + | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 PubMed] | + | #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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4990 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23897964 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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. [https://www.nature.com/articles/leu2015306 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26522083 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26549589 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. [https://www.nature.com/articles/leu2015306 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26522083 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26549589 PubMed] | ||
<!-- # '''Abstract:''' R. M. Stone, H. Dohner, G. Ehninger, M. Villeneuve, T. Teasdale, J. D. Virkus, L. R. Bressler, M. M. Seiler, G. Marcucci, R. A. Larson. CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. 2011 ASCO Annual Meeting abstract TPS199. [http://meetinglibrary.asco.org/content/81555-102 link to abstract] | <!-- # '''Abstract:''' R. M. Stone, H. Dohner, G. Ehninger, M. Villeneuve, T. Teasdale, J. D. Virkus, L. R. Bressler, M. M. Seiler, G. Marcucci, R. A. Larson. CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. 2011 ASCO Annual Meeting abstract TPS199. [http://meetinglibrary.asco.org/content/81555-102 link to abstract] | ||
# '''Abstract:''' Richard M. Stone, Sumithra Mandrekar, Ben L Sanford, Susan Geyer, Clara D. Bloomfield, Konstanze Dohner, Christian Thiede, Guido Marcucci, Francesco Lo-Coco, Rebecca B. Klisovic, Andrew Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S Tallman, Jurgen Krauter, Richard F. Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A. Larson, Hartmut Dohner. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). 2015 ASH Annual Meeting plenary abstract 6. [https://ash.confex.com/ash/2015/webprogramscheduler/Paper80269.html link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT00651261 Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (NCT00651261) at ClinicalTrials.gov] --> | # '''Abstract:''' Richard M. Stone, Sumithra Mandrekar, Ben L Sanford, Susan Geyer, Clara D. Bloomfield, Konstanze Dohner, Christian Thiede, Guido Marcucci, Francesco Lo-Coco, Rebecca B. Klisovic, Andrew Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S Tallman, Jurgen Krauter, Richard F. Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A. Larson, Hartmut Dohner. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). 2015 ASH Annual Meeting plenary abstract 6. [https://ash.confex.com/ash/2015/webprogramscheduler/Paper80269.html link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT00651261 Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (NCT00651261) at ClinicalTrials.gov] --> | ||
− | # '''RATIFY:''' Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. [https://www.nejm.org/doi/full/10.1056/NEJMoa1614359 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754190/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28644114 PubMed] | + | #'''RATIFY:''' Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. [https://www.nejm.org/doi/full/10.1056/NEJMoa1614359 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754190/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28644114 PubMed] |
<!-- # '''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 [http://ascopubs.org/doi/abs/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 [http://ascopubs.org/doi/abs/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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | + | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] |
==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}== | ==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}== | ||
Line 434: | Line 453: | ||
|} | |} | ||
====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 | ||
Line 439: | Line 459: | ||
'''7-day course''' | '''7-day course''' | ||
====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]] | ||
Line 455: | Line 476: | ||
|} | |} | ||
====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 | ||
Line 484: | Line 506: | ||
|} | |} | ||
====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 | ||
Line 489: | Line 512: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]] | *HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]] | ||
*COSAH C-022, with CR: [[#HiDAC|HiDAC consolidation]] if good- or intermediate-risk cytogenetics, or cytarabine & etoposide consolidation if high-risk cytogenetics. | *COSAH C-022, with CR: [[#HiDAC|HiDAC consolidation]] if good- or intermediate-risk cytogenetics, or cytarabine & etoposide consolidation if high-risk cytogenetics. | ||
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15142880 PubMed] |
− | # '''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 PubMed] |
− | ## '''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. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed] | + | #'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 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. [http://www.bloodjournal.org/content/118/14/3832.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21828126 PubMed] | + | ##'''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. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 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. [http://www.bloodjournal.org/content/118/14/3832.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21828126 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 PubMed] |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | ||
==7+3d & GO {{#subobject:869f84|Regimen=1}}== | ==7+3d & GO {{#subobject:869f84|Regimen=1}}== | ||
Line 521: | Line 546: | ||
|} | |} | ||
====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 | ||
Line 527: | Line 553: | ||
'''7-day course''' | '''7-day course''' | ||
====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]] | ||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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://www.ncbi.nlm.nih.gov/pubmed/30076173 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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://www.ncbi.nlm.nih.gov/pubmed/30076173 PubMed] | ||
==7+3i {{#subobject:717935|Regimen=1}}== | ==7+3i {{#subobject:717935|Regimen=1}}== | ||
Line 556: | Line 584: | ||
|} | |} | ||
====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 | ||
Line 600: | Line 629: | ||
|} | |} | ||
====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 | ||
Line 621: | Line 651: | ||
|} | |} | ||
====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 | ||
Line 660: | Line 691: | ||
|} | |} | ||
====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 | ||
Line 666: | Line 698: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*HOVON/SAKK AML 29 & AML 42: Amsacrine & Cytarabine | *HOVON/SAKK AML 29 & AML 42: 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]] | ||
− | *COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: [[#HiDAC|HiDAC consolidation]] | + | *COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: [[#HiDAC|HiDAC consolidation]] |
*COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE consolidation]] | *COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE consolidation]] | ||
Line 685: | Line 718: | ||
|} | |} | ||
====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 | ||
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'''7-day course''' | '''7-day course''' | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 PubMed] | + | |
− | # Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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. [http://ascopubs.org/doi/10.1200/JCO.1992.10.7.1103 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1607916 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 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. [https://www.ncbi.nlm.nih.gov/pubmed/8290968 PubMed] | + | #Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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. [http://ascopubs.org/doi/10.1200/JCO.1992.10.7.1103 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1607916 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 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. [https://www.ncbi.nlm.nih.gov/pubmed/8290968 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa025406 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12930926 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa025406 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12930926 PubMed] |
− | # '''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 AML 97 Study. 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. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.21493 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16284985 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.23.2652 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20048183 PubMed] | + | #'''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 AML 97 Study. 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. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.21493 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16284985 PubMed] |
− | # '''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. [https://link.springer.com/article/10.1007%2Fs12185-009-0480-5 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20054669 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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.23.2652 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20048183 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. [http://www.bloodjournal.org/content/117/8/2358 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20693429 PubMed] | + | #'''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. [https://link.springer.com/article/10.1007%2Fs12185-009-0480-5 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20054669 PubMed] |
− | # '''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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. [https://www.nejm.org/doi/full/10.1056/NEJMoa1010222 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21410371 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. [http://www.bloodjournal.org/content/117/8/2358 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20693429 PubMed] |
− | # '''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 protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed] | + | #'''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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. [https://www.nejm.org/doi/full/10.1056/NEJMoa1010222 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21410371 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | + | #'''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 protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed] |
− | # 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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (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. [http://www.bloodjournal.org/content/129/12/1636.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28049642 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | + | #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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (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. [http://www.bloodjournal.org/content/129/12/1636.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28049642 PubMed] |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | ||
==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}== | ==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}== | ||
Line 723: | Line 758: | ||
''Note: Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ''Note: Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 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>) | *[[Cytarabine (Ara-C)]] 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>) | ||
**Patients older than 60 received: 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>) | **Patients older than 60 received: 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>) | ||
Line 730: | Line 766: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib consolidation]] | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib consolidation]] | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | # 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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | + | #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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | ||
==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}== | ==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}== | ||
Line 753: | Line 791: | ||
|} | |} | ||
====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 | ||
Line 759: | Line 798: | ||
'''28-day course''' | '''28-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#IDAC|Cytarabine consolidation]] | *[[#IDAC|Cytarabine consolidation]] | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30074259 PubMed] | + | |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30074259 PubMed] | ||
==7+3m {{#subobject:240c72|Regimen=1}}== | ==7+3m {{#subobject:240c72|Regimen=1}}== | ||
Line 785: | Line 826: | ||
|} | |} | ||
====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 | ||
Line 790: | Line 832: | ||
'''7-day course''' | '''7-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3m | *Patients with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3m | ||
===References=== | ===References=== | ||
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 PubMed] | ||
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}== | ==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}== | ||
Line 818: | Line 862: | ||
|} | |} | ||
====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 | ||
Line 838: | Line 883: | ||
|} | |} | ||
====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 | ||
Line 844: | Line 890: | ||
'''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''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*5-2-5 consolidation x 2 | *5-2-5 consolidation x 2 | ||
Line 871: | Line 918: | ||
''Note: these trials have complicated treatment schemas; see papers for details.'' | ''Note: these trials have complicated treatment schemas; see papers for details.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5 induction]] | *[[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5 induction]] | ||
====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 | ||
Line 880: | Line 929: | ||
'''8-day course''' | '''8-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*UK MRC AML10: MACE consolidation | *UK MRC AML10: MACE consolidation | ||
*Other trials: Consolidation (see paper for details) | *Other trials: Consolidation (see paper for details) | ||
Line 897: | Line 947: | ||
|} | |} | ||
====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 | ||
Line 917: | Line 968: | ||
|} | |} | ||
====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 | ||
Line 953: | Line 1,005: | ||
''Note: these trials have complicated treatment schemas; see papers for details.'' | ''Note: these trials have complicated treatment schemas; see papers for details.'' | ||
====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 | ||
Line 959: | Line 1,012: | ||
'''10-day course''' | '''10-day course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*ADE 8-3-5 | *ADE 8-3-5 | ||
===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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9116274 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8634416 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)09214-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9504514 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9116274 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. [http://www.bloodjournal.org/content/93/12/4131.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10361110 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)09214-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9504514 PubMed] |
− | ## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.22.9088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20038732 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. [http://www.bloodjournal.org/content/93/12/4131.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10361110 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. [http://www.bloodjournal.org/content/100/4/1224.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149202 PubMed] | + | ##'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.22.9088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20038732 PubMed] |
− | ## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0472 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652081/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18591543 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. [http://www.bloodjournal.org/content/100/4/1224.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149202 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. 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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.20.6490 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773224/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19826132 PubMed] | + | ##'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0472 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652081/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18591543 PubMed] |
− | # '''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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. 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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.20.6490 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773224/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19826132 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed] | + | #'''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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 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. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 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. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 PubMed] |
− | # '''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [http://ascopubs.org/doi/full/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25092781 PubMed] | + | #'''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [http://ascopubs.org/doi/full/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25092781 PubMed] |
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}== | ==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}== | ||
Line 998: | Line 1,053: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (8 doses per cycle) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (8 doses per cycle) | ||
*[[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 | ||
Line 1,018: | Line 1,074: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (8 doses per cycle) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (8 doses per cycle) | ||
*[[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 | ||
Line 1,024: | Line 1,081: | ||
'''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''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*5-2-5 consolidation x 2 | *5-2-5 consolidation x 2 | ||
===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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 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. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 PubMed] |
==CIA {{#subobject:de6dec|Regimen=1}}== | ==CIA {{#subobject:de6dec|Regimen=1}}== | ||
Line 1,039: | Line 1,098: | ||
===Variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}=== | ===Variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ Jabbour et al. 2017] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ Jabbour et al. 2017] | ||
Line 1,051: | Line 1,110: | ||
|} | |} | ||
====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 | ||
Line 1,057: | Line 1,117: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients not achieving CR or CRp could undergo a second induction | *Patients not achieving CR or CRp could undergo a second induction | ||
*Patients achieving CR or CRp: [[#CIA_2|CIA consolidation]] | *Patients achieving CR or CRp: [[#CIA_2|CIA consolidation]] | ||
Line 1,070: | Line 1,131: | ||
|} | |} | ||
====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 | ||
Line 1,075: | Line 1,137: | ||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*[[Levofloxacin (Levaquin)]] | *[[Levofloxacin (Levaquin)]] | ||
*[[Itraconazole (Sporanox)]] | *[[Itraconazole (Sporanox)]] | ||
Line 1,082: | Line 1,145: | ||
'''5-day course''' | '''5-day course''' | ||
====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]] | ||
===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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed] | + | |
− | # 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://onlinelibrary.wiley.com/doi/10.1002/cncr.30883/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28708931 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed] |
+ | #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://onlinelibrary.wiley.com/doi/10.1002/cncr.30883/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28708931 PubMed] | ||
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}== | ==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}== | ||
Line 1,115: | Line 1,180: | ||
''Both trials have complicated treatment schemas; see papers for details.'' | ''Both trials have complicated treatment schemas; see papers for details.'' | ||
====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 | ||
Line 1,121: | Line 1,187: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*See paper for details (to be completed). | *See paper for details (to be completed). | ||
===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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed] | + | #'''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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 PubMed] | ||
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}== | ==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}== | ||
Line 1,156: | Line 1,224: | ||
''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.'' | ||
====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 | ||
Line 1,161: | Line 1,230: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*See papers for details (to be completed). | *See papers for details (to be completed). | ||
Line 1,178: | Line 1,248: | ||
''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.'' | ||
====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 | ||
Line 1,183: | Line 1,254: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Complex randomization; see paper for details (to be completed). | *Complex randomization; see paper for details (to be completed). | ||
===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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed] | + | #'''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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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/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. [http://www.bloodjournal.org/content/125/25/3878.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25833957 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 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/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. [http://www.bloodjournal.org/content/125/25/3878.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25833957 PubMed] | ||
==DAC {{#subobject:9b1553|Regimen=1}}== | ==DAC {{#subobject:9b1553|Regimen=1}}== | ||
Line 1,221: | Line 1,294: | ||
|} | |} | ||
====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>) | ||
Line 1,226: | Line 1,300: | ||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*"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 | ||
Line 1,231: | Line 1,306: | ||
'''7-day course''' | '''7-day course''' | ||
====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 [[#HiDAC|HiDAC]] consolidation | *Patients in remission in both studies: [[#HAM|HAM]], then [[#HiDAC|HiDAC]] consolidation | ||
===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 (PALG). 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://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 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 (PALG). 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://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed] | ||
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}== | ==FLAG-Ida {{#subobject:7fc219|Regimen=1}}== | ||
Line 1,256: | Line 1,333: | ||
''This trial has a complex randomization; to be completed.'' | ''This trial has a complex randomization; to be completed.'' | ||
====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''' | ||
Line 1,263: | Line 1,341: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*See paper for details | *See paper for details | ||
+ | |||
===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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed] | + | #'''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. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 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. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed] | ||
==HAA {{#subobject:0788e0|Regimen=1}}== | ==HAA {{#subobject:0788e0|Regimen=1}}== | ||
Line 1,292: | Line 1,373: | ||
''Unlikely to be completed since there were significantly more deaths in this arm, despite a superior primary efficacy endpoint.'' | ''Unlikely to be completed since there were significantly more deaths in this arm, despite a superior primary efficacy endpoint.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Omacetaxine (Synribo)]] | *[[Omacetaxine (Synribo)]] | ||
*[[Cytarabine (Ara-C)]] | *[[Cytarabine (Ara-C)]] | ||
*[[Aclarubicin (Aclacinon)]] | *[[Aclarubicin (Aclacinon)]] | ||
+ | |||
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed] | + | |
+ | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed] | ||
==HAD {{#subobject:30f8fa|Regimen=1}}== | ==HAD {{#subobject:30f8fa|Regimen=1}}== | ||
Line 1,322: | Line 1,406: | ||
''Unlikely to be completed since there were significantly more deaths in this arm, despite a trend towards a superior primary efficacy endpoint.'' | ''Unlikely to be completed since there were significantly more deaths in this arm, despite a trend towards a superior primary efficacy endpoint.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Omacetaxine (Synribo)]] | *[[Omacetaxine (Synribo)]] | ||
*[[Cytarabine (Ara-C)]] | *[[Cytarabine (Ara-C)]] | ||
*[[Daunorubicin (Cerubidine)]] | *[[Daunorubicin (Cerubidine)]] | ||
+ | |||
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed] | + | |
+ | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed] | ||
==ICE (Idarubicin) {{#subobject:948b49|Regimen=1}}== | ==ICE (Idarubicin) {{#subobject:948b49|Regimen=1}}== | ||
Line 1,373: | Line 1,460: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[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 | ||
*[[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>) | ||
Line 1,379: | Line 1,467: | ||
'''One course''' | '''One course''' | ||
====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 | ||
+ | |||
===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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/15385923 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://www.ncbi.nlm.nih.gov/pubmed/15213095 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. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2005.05745.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16197446 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://www.ncbi.nlm.nih.gov/pubmed/15385923 PubMed] |
− | # '''EORTC 58921:''' Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; EORTC Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. [https://www.nature.com/articles/2403932 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16136166 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. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2005.05745.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16197446 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. [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://www.ncbi.nlm.nih.gov/pubmed/20494931 PubMed] | + | #'''EORTC 58921:''' Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; EORTC Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. [https://www.nature.com/articles/2403932 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16136166 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30948365 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. [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://www.ncbi.nlm.nih.gov/pubmed/20494931 PubMed] |
+ | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30948365 PubMed] | ||
==ICL {{#subobject:a904d7|Regimen=1}}== | ==ICL {{#subobject:a904d7|Regimen=1}}== | ||
Line 1,408: | Line 1,499: | ||
|} | |} | ||
====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>) | ||
Line 1,414: | Line 1,506: | ||
'''One course''' | '''One course''' | ||
====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]] | ||
===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. [http://ascopubs.org/doi/10.1200/JCO.2018.78.7366 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30260758 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/10.1200/JCO.2018.78.7366 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30260758 PubMed] | ||
==MEC {{#subobject:324735|Regimen=1}}== | ==MEC {{#subobject:324735|Regimen=1}}== | ||
Line 1,445: | Line 1,539: | ||
|} | |} | ||
====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 | ||
Line 1,452: | Line 1,547: | ||
===References=== | ===References=== | ||
− | # '''EORTC/GIMEMA AML-13:''' 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2013.49.0771 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24127442 PubMed] | + | #'''EORTC/GIMEMA AML-13:''' 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2013.49.0771 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24127442 PubMed] | ||
=First-line induction therapy, older or "unfit" patients= | =First-line induction therapy, older or "unfit" patients= | ||
Line 1,481: | Line 1,577: | ||
|} | |} | ||
====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 | ||
Line 1,486: | Line 1,583: | ||
===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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.23.8329 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20026804 PubMed] | + | |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed] | + | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.23.8329 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20026804 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | ||
==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}== | ==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}== | ||
Line 1,508: | Line 1,606: | ||
====Chemotherapy, induction==== | ====Chemotherapy, induction==== | ||
+ | |||
*[[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 | ||
*[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | *[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | ||
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30010-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. 2018 Oct 25. [Epub ahead of print] [http://www.bloodjournal.org/content/133/1/7 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30361262 PubMed] | + | #'''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30010-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. 2018 Oct 25. [Epub ahead of print] [http://www.bloodjournal.org/content/133/1/7 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30361262 PubMed] | ||
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}== | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}== | ||
Line 1,536: | Line 1,636: | ||
====Supportive medications, pre-treatment phase==== | ====Supportive medications, 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 | ||
Line 1,541: | Line 1,642: | ||
====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 | ||
*[[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 medications==== | ====Supportive medications==== | ||
+ | |||
*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]] | ||
'''One cycle''' | '''One cycle''' | ||
====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 | ||
===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://www.tandfonline.com/doi/full/10.1080/10428190802451254 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.tandfonline.com/doi/full/10.1080/10428190802451254 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 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. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed] |
==Best supportive care== | ==Best supportive care== | ||
Line 1,598: | Line 1,703: | ||
===References=== | ===References=== | ||
− | # Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, Cauchie C, Peetermans M, Solbu G, Suciu S, Stryckmans P. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989 Sep;7(9):1268-74. [http://ascopubs.org/doi/abs/10.1200/JCO.1989.7.9.1268 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2475589 PubMed] | + | |
− | # '''FIGHT-AML-301:''' Harousseau JL, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, Ossenkoppele GJ, Alexeeva JA, Beutel G, Maertens J, Vidriales MB, Dombret H, Thomas X, Burnett AK, Robak T, Khuageva NK, Golenkov AK, Tothova E, Mollgard L, Park YC, Bessems A, De Porre P, Howes AJ; FIGHT-AML-301 Investigators. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009 Aug 6;114(6):1166-73. Epub 2009 May 21. [http://www.bloodjournal.org/content/114/6/1166.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19470696 PubMed] | + | #Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, Cauchie C, Peetermans M, Solbu G, Suciu S, Stryckmans P. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989 Sep;7(9):1268-74. [http://ascopubs.org/doi/abs/10.1200/JCO.1989.7.9.1268 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2475589 PubMed] |
+ | #'''FIGHT-AML-301:''' Harousseau JL, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, Ossenkoppele GJ, Alexeeva JA, Beutel G, Maertens J, Vidriales MB, Dombret H, Thomas X, Burnett AK, Robak T, Khuageva NK, Golenkov AK, Tothova E, Mollgard L, Park YC, Bessems A, De Porre P, Howes AJ; FIGHT-AML-301 Investigators. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009 Aug 6;114(6):1166-73. Epub 2009 May 21. [http://www.bloodjournal.org/content/114/6/1166.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19470696 PubMed] | ||
<!-- 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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 PubMed] | + | #'''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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29417613 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] |
<!-- 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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] | + | #'''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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] |
==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}== | ==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}== | ||
Line 1,628: | Line 1,734: | ||
''Note: reported efficacy is based on the 2013 update.'' | ''Note: reported efficacy is based on the 2013 update.'' | ||
====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 | ||
Line 1,651: | Line 1,758: | ||
|} | |} | ||
====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 | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *A second induction was permitted for SD or better. | + | |
+ | *A second induction was permitted for SD or better. | ||
*Faderl et al. 2008: Responders proceeded to clofarabine & cytarabine consolidation | *Faderl et al. 2008: Responders proceeded to clofarabine & cytarabine consolidation | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 PubMed] | + | |
− | # 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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.26.4242 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20385984 PubMed] | + | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 PubMed] | + | #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. [http://ascopubs.org/doi/full/10.1200/JCO.2009.26.4242 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20385984 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 PubMed] | ||
==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}== | ==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}== | ||
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|} | |} | ||
====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''' | ||
Line 1,690: | Line 1,801: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*A second induction was permitted for SD or better | *A second induction was permitted for SD or better | ||
*Responders proceeded to clofarabine & cytarabine consolidation | *Responders proceeded to clofarabine & cytarabine consolidation | ||
Line 1,703: | Line 1,815: | ||
|} | |} | ||
====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 | ||
Line 1,708: | Line 1,821: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients not achieving CR could undergo an identical second induction after at least 28 days. | *Patients not achieving CR could undergo an identical second induction after at least 28 days. | ||
**Patients not achieving CR after the second induction were given [[#Decitabine_monotherapy_3|salvage decitabine]] | **Patients not achieving CR after the second induction were given [[#Decitabine_monotherapy_3|salvage decitabine]] | ||
Line 1,713: | Line 1,827: | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 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://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22282348 PubMed] | + | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 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://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 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://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 PubMed] | ||
==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}== | ==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}== | ||
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|} | |} | ||
====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 | ||
Line 1,748: | Line 1,864: | ||
'''One or two courses''' | '''One or two courses''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*CR/CRi: [[#CPX-351_monotherapy_2|CPX-351 monotherapy consolidation]] | *CR/CRi: [[#CPX-351_monotherapy_2|CPX-351 monotherapy consolidation]] | ||
===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://bloodjournal.hematologylibrary.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24687088 PubMed] | + | |
+ | #'''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://bloodjournal.hematologylibrary.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24687088 PubMed] | ||
<!-- # '''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 [http://ascopubs.org/doi/abs/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 [http://ascopubs.org/doi/abs/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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | + | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] |
==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}== | ==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}== | ||
Line 1,776: | Line 1,894: | ||
|} | |} | ||
====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 | ||
Line 1,794: | Line 1,913: | ||
|} | |} | ||
====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 medications==== | ====Supportive medications==== | ||
+ | |||
*[[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 | ||
Line 1,814: | Line 1,935: | ||
|} | |} | ||
====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 medications==== | ====Supportive medications==== | ||
+ | |||
*[[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''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Blum et al. 2010, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above | *Blum et al. 2010, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above | ||
*Blum et al. 2010, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine maintenance]] | *Blum et al. 2010, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine maintenance]] | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed] | + | |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed] | ||
<!-- 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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 PubMed] | + | #'''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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29417613 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29085/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25336333 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29085/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25336333 PubMed] |
− | # 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1605949#article_supplementary_material link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217532/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27959731 PubMed] | + | #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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1605949#article_supplementary_material link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217532/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27959731 PubMed] |
==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}== | ==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}== | ||
Line 1,850: | Line 1,975: | ||
====Chemotherapy, induction==== | ====Chemotherapy, induction==== | ||
+ | |||
*[[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 | ||
*[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | *[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | ||
Line 1,866: | Line 1,992: | ||
====Chemotherapy, induction==== | ====Chemotherapy, induction==== | ||
+ | |||
*[[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 | ||
*[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | *[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day | ||
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30010-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.bloodjournal.org/content/133/1/7 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30361262 PubMed] | + | #'''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30010-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.bloodjournal.org/content/133/1/7 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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] | ||
Line 1,893: | Line 2,021: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[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 | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin maintenance]] | *Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin maintenance]] | ||
===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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] | + | |
+ | #'''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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] | ||
==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}== | ==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}== | ||
Line 1,923: | Line 2,054: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Glasdegib (Daurismo)]] 100 mg PO once per day | *[[Glasdegib (Daurismo)]] 100 mg PO once per day | ||
*[[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 | ||
Line 1,929: | Line 2,061: | ||
===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 verified protocol''' --> | <!-- # '''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 verified protocol''' --> | ||
− | # '''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://www.ncbi.nlm.nih.gov/pubmed/30555165 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. [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://www.ncbi.nlm.nih.gov/pubmed/30555165 PubMed] | ||
==LoDAC {{#subobject:25e1c6|Regimen=1}}== | ==LoDAC {{#subobject:25e1c6|Regimen=1}}== | ||
Line 1,962: | Line 2,095: | ||
|} | |} | ||
====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 | ||
Line 2,004: | Line 2,138: | ||
''Note: reported efficacy for UK NCRI AML16 is based on the 2016 update.'' | ''Note: reported efficacy for UK NCRI AML16 is based on the 2016 update.'' | ||
====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 | ||
Line 2,022: | Line 2,157: | ||
|} | |} | ||
====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 | ||
Line 2,028: | Line 2,164: | ||
===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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29417613 PubMed] | + | #'''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. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 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. [http://www.haematologica.org/content/98/1/119.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533673/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22801961 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://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25062 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29417613 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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. [http://www.haematologica.org/content/98/1/119.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533673/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22801961 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 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. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132839/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23605952 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://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 PubMed] |
− | # '''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. [http://www.bloodjournal.org/content/124/9/1426.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148765/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25006120 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. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132839/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23605952 PubMed] |
− | # 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. [http://www.bloodjournal.org/content/125/19/2923.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25805811 PubMed] | + | #'''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. [http://www.bloodjournal.org/content/124/9/1426.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148765/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25006120 PubMed] |
− | # 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. [https://www.nature.com/leu/journal/v29/n6/full/leu201538a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25676423 PubMed] | + | #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. [http://www.bloodjournal.org/content/125/19/2923.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25805811 PubMed] |
− | # '''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed] | + | #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. [https://www.nature.com/leu/journal/v29/n6/full/leu201538a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25676423 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed] | + | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 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. [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://www.ncbi.nlm.nih.gov/pubmed/30555165 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://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 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. [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://www.ncbi.nlm.nih.gov/pubmed/30555165 PubMed] | ||
==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}== | ==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}== | ||
Line 2,053: | Line 2,190: | ||
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://ascopubs.org/doi/full/10.1200/JCO.18.01600?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed Wei et. al. 2019 (M14-387)] |
| style="background-color:#91cf61" |Phase II | | style="background-color:#91cf61" |Phase II | ||
|- | |- | ||
|} | |} | ||
− | + | <br /> | |
====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 | ||
− | *[[Venetoclax (Venclexta)]] 600 mg PO once per day | + | *[[Venetoclax (Venclexta)]] 600 mg PO once per day (dose reduction indicated when used when with CYP3A inhibitors) |
'''28-day cycles''' | '''28-day cycles''' | ||
===References=== | ===References=== | ||
− | + | ===1. Wei AH, Strickland Jr SA, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. Journal of Clinical Oncology. 2019 Mar 20:JCO-18. [https://ascopubs.org/doi/full/10.1200/JCO.18.01600?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed link to abstract] '''contains protocol'''=== | |
− | # [https://clinicaltrials.gov/ct2/show/NCT02287233 NCT02287233] '''contains protocol''' | + | |
+ | #[https://clinicaltrials.gov/ct2/show/NCT02287233 NCT02287233] '''contains protocol''' | ||
==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}== | ||
Line 2,085: | Line 2,224: | ||
''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.'' | ||
====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''' | ||
===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://onlinelibrary.wiley.com/doi/10.1111/bjh.13094/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1111/bjh.13094/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25160658 PubMed] | ||
=Consolidation after upfront therapy= | =Consolidation after upfront therapy= | ||
Line 2,109: | Line 2,250: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] | *[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] | ||
====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 | ||
Line 2,119: | Line 2,262: | ||
===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 [http://ascopubs.org/doi/abs/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 [http://ascopubs.org/doi/abs/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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | ||
==HiDAC {{#subobject:caa3a2|Regimen=1}}== | ==HiDAC {{#subobject:caa3a2|Regimen=1}}== | ||
Line 2,140: | Line 2,284: | ||
''Details in the text are scant.'' | ''Details in the text are scant.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Cytarabine_.26_Mitoxantrone|Cytarabine & Mitoxantrone consolidation]] | *[[#Cytarabine_.26_Mitoxantrone|Cytarabine & Mitoxantrone consolidation]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (6 total doses) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (6 total doses) | ||
Line 2,158: | Line 2,305: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*BHAC-MMV | *BHAC-MMV | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses) | ||
'''2 cycles''' | '''2 cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*A-VVV | *A-VVV | ||
Line 2,180: | Line 2,331: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*5+2i | *5+2i | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (12 total doses) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (12 total doses) | ||
Line 2,226: | Line 2,380: | ||
''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.'' | ||
====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 2,232: | Line 2,387: | ||
*SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] versus 7+3d & Sorafenib | *SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] versus 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]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | ||
'''3 cycles of varying durations''' | '''3 cycles of varying durations''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*SWOG S0106: GO maintenance versus [[#Observation|no further treatment]] | *SWOG S0106: GO maintenance versus [[#Observation|no further treatment]] | ||
Line 2,254: | Line 2,412: | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*7+5d or [[#7.2B3i|7+3i]] | *7+5d or [[#7.2B3i|7+3i]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (10 total doses) | ||
Line 2,284: | Line 2,445: | ||
|} | |} | ||
====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]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | ||
'''Up to 4 cycles''' | '''Up to 4 cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*ALFA-9802: Cytarabine & Daunorubicin maintenance | *ALFA-9802: Cytarabine & Daunorubicin maintenance | ||
+ | |||
===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; Cancer and Leukemia Group B. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://www.nejm.org/doi/full/10.1056/NEJM199410063311402 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/10.1056/NEJM199812033392301 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9834301 PubMed] | + | #'''CALGB 8525:''' Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; Cancer and Leukemia Group B. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://www.nejm.org/doi/full/10.1056/NEJM199410063311402 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8078551 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. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 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://www.nejm.org/doi/10.1056/NEJM199812033392301 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9834301 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. [http://www.bloodjournal.org/content/117/8/2358 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20693429 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. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 PubMed] |
− | ## '''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. [http://www.bloodjournal.org/content/117/8/2366.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21190996 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. [http://www.bloodjournal.org/content/117/8/2358 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20693429 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. [http://www.bloodjournal.org/content/118/7/1754.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21690555 PubMed] | + | ##'''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. [http://www.bloodjournal.org/content/117/8/2366.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21190996 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22287757 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. [http://www.bloodjournal.org/content/118/7/1754.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21690555 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22287757 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed] | + | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26549589 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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26549589 PubMed] |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | ||
==IDAC {{#subobject:f5cd74|Regimen=1}}== | ==IDAC {{#subobject:f5cd74|Regimen=1}}== | ||
Line 2,325: | Line 2,492: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Amonafide & Cytarabine versus [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]] | *Amonafide & Cytarabine versus [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]] | ||
*7+3d & Glasdegib | *7+3d & Glasdegib | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (3 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (3 total doses) | ||
Line 2,344: | Line 2,514: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*BHAC-MMV | *BHAC-MMV | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses) | ||
'''Two cycles''' | '''Two cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*A-VVV | *A-VVV | ||
Line 2,362: | Line 2,536: | ||
|} | |} | ||
====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)]] | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (12 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (12 total doses) | ||
'''One cycle''' | '''One cycle''' | ||
====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 [[#Observation|no further treatment]] | *Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[#Observation|no further treatment]] | ||
===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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22287757 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed] | ||
==HDAC & G-CSF {{#subobject:e0396d|Regimen=1}}== | ==HDAC & G-CSF {{#subobject:e0396d|Regimen=1}}== | ||
Line 2,398: | Line 2,576: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Cytarabine, Daunorubicin, G-CSF induction | *Cytarabine, Daunorubicin, G-CSF induction | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (6 total doses) | ||
*[[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 | ||
Line 2,406: | Line 2,587: | ||
===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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed] | ||
==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}== | ||
Line 2,423: | Line 2,605: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin consolidation]] | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin consolidation]] | ||
+ | |||
====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 | ||
Line 2,431: | Line 2,616: | ||
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 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. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed] | ||
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}== | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}== | ||
Line 2,448: | Line 2,634: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin induction]] | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin induction]] | ||
+ | |||
====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 | ||
*[[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 medications==== | ====Supportive medications==== | ||
+ | |||
*"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 | ||
Line 2,459: | Line 2,649: | ||
'''1 cycle''' | '''1 cycle''' | ||
====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 | ||
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 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. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed] | ||
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}== | ==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}== | ||
Line 2,485: | Line 2,677: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3i|7+3i]], then amsacrine & cytarabine | *[[#7.2B3i|7+3i]], then amsacrine & cytarabine | ||
{{#lst:Autologous HSCT|6ccf66}} | {{#lst:Autologous HSCT|6ccf66}} | ||
Line 2,501: | Line 2,694: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3d_.28standard-dose.29|7+3d]], then [[#HiDAC|HiDAC]] | *[[#7.2B3d_.28standard-dose.29|7+3d]], then [[#HiDAC|HiDAC]] | ||
{{#lst:Autologous HSCT|5d4efb}} | {{#lst:Autologous HSCT|5d4efb}} | ||
===References=== | ===References=== | ||
− | # Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. [https://www.nejm.org/doi/10.1056/NEJM199605303342203 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8618581 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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21951683 PubMed] | + | #Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. [https://www.nejm.org/doi/10.1056/NEJM199605303342203 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8618581 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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21951683 PubMed] | ||
==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}== | ==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}== | ||
Line 2,525: | Line 2,720: | ||
===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. --> | ||
− | # 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. [http://jco.ascopubs.org/content/33/35/4167.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26527780 PubMed] | + | |
+ | #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. [http://jco.ascopubs.org/content/33/35/4167.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26527780 PubMed] | ||
==CIA {{#subobject:db5c09|Regimen=1}}== | ==CIA {{#subobject:db5c09|Regimen=1}}== | ||
Line 2,543: | Line 2,739: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#CIA|CIA induction]] | *[[#CIA|CIA induction]] | ||
+ | |||
====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 | ||
Line 2,552: | Line 2,751: | ||
===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://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed] | ||
==CLARA {{#subobject:6160cf|Regimen=1}}== | ==CLARA {{#subobject:6160cf|Regimen=1}}== | ||
Line 2,574: | Line 2,774: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Cytarabine, Daunorubicin, G-CSF induction | *Cytarabine, Daunorubicin, G-CSF induction | ||
+ | |||
====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''' | ||
Line 2,583: | Line 2,786: | ||
===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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed] | ||
==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}== | ==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}== | ||
Line 2,601: | Line 2,805: | ||
|} | |} | ||
====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. | ||
====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 | ||
Line 2,612: | Line 2,818: | ||
====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 | ||
Line 2,618: | Line 2,825: | ||
===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://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 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://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 PubMed] | ||
==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}== | ==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}== | ||
Line 2,637: | Line 2,845: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#CPX-351_monotherapy|CPX-351 monotherapy induction]] | *[[#CPX-351_monotherapy|CPX-351 monotherapy induction]] | ||
+ | |||
====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 | ||
Line 2,645: | Line 2,856: | ||
===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 [http://ascopubs.org/doi/abs/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 [http://ascopubs.org/doi/abs/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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30024784 PubMed] | ||
==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}== | ==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}== | ||
Line 2,663: | Line 2,875: | ||
''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. Length of courses is not specified.'' | ''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. Length of courses is not specified.'' | ||
====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 | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses) | ||
*[[Daunorubicin (Cerubidine)]] as follows: | *[[Daunorubicin (Cerubidine)]] as follows: | ||
Line 2,686: | Line 2,901: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*4d + 7 induction | *4d + 7 induction | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses) | ||
*[[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 | ||
Line 2,694: | Line 2,912: | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed] | + | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 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://www.ncbi.nlm.nih.gov/pubmed/30076173 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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://www.ncbi.nlm.nih.gov/pubmed/30076173 PubMed] | ||
==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}== | ==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}== | ||
Line 2,714: | Line 2,933: | ||
''Note: length of courses is not specified.'' | ''Note: length of courses is not specified.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3d_.26_GO|7+3d & GO]] induction | *[[#7.2B3d_.26_GO|7+3d & GO]] induction | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses) | ||
*[[Daunorubicin (Cerubidine)]] as follows: | *[[Daunorubicin (Cerubidine)]] as follows: | ||
Line 2,726: | Line 2,947: | ||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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://www.ncbi.nlm.nih.gov/pubmed/30076173 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 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://www.ncbi.nlm.nih.gov/pubmed/30076173 PubMed] | ||
==CYVE {{#subobject:f8d436|Regimen=1}}== | ==CYVE {{#subobject:f8d436|Regimen=1}}== | ||
Line 2,746: | Line 2,968: | ||
''Note: this consolidation regimen was for patients with high-risk cytogenetics.'' | ''Note: this consolidation regimen was for patients with high-risk cytogenetics.'' | ||
====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="width:100%; overflow:auto;"> | <div class="toccolours" style="width:100%; overflow:auto;"> | ||
====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 | ||
Line 2,755: | Line 2,979: | ||
</div> | </div> | ||
====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) | ||
===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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed] | ||
==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}== | ==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}== | ||
Line 2,779: | Line 3,005: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*4i + 7 induction | *4i + 7 induction | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses) | ||
*[[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 | ||
Line 2,787: | Line 3,016: | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 PubMed] | + | |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 PubMed] | ||
==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}== | ==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}== | ||
Line 2,805: | Line 3,035: | ||
''Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ''Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib induction]] | *[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib induction]] | ||
+ | |||
====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 | ||
Line 2,813: | Line 3,046: | ||
'''4 to 6-week cycle for up to 5 cycles''' | '''4 to 6-week cycle for up to 5 cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#Sorafenib_monotherapy|Sorafenib maintenance]] | *[[#Sorafenib_monotherapy|Sorafenib maintenance]] | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | # 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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | + | #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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | ||
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}== | ==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}== | ||
Line 2,828: | Line 3,063: | ||
===Regimen {{#subobject:6ca28d|Variant=1}}=== | ===Regimen {{#subobject:6ca28d|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 20%"|Study | + | ! style="width: 20%" |Study |
− | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 20%"|Comparator | + | ! style="width: 20%" |Comparator |
− | !style="width: 20%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
− | !style="width: 20%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] |
|- | |- | ||
|[https://www.nejm.org/doi/full/10.1056/NEJM198005083021901 Blume et al. 1980] | |[https://www.nejm.org/doi/full/10.1056/NEJM198005083021901 Blume et al. 1980] | ||
Line 2,860: | Line 3,095: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then amsacrine & IDAC | *Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then amsacrine & IDAC | ||
{{#lst:Allogeneic HSCT|6ca28d}} | {{#lst:Allogeneic HSCT|6ca28d}} | ||
===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://www.nejm.org/doi/full/10.1056/NEJM198005083021901 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6245359 PubMed] | + | |
− | # Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. [https://www.nejm.org/doi/full/10.1056/NEJM198712243172602 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3317056 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://www.nejm.org/doi/full/10.1056/NEJM198005083021901 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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; European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. 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://www.nejm.org/doi/full/10.1056/NEJM199501263320403 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7808487 PubMed] | + | #Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. [https://www.nejm.org/doi/full/10.1056/NEJM198712243172602 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3317056 PubMed] |
− | # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22959335 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; European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. 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://www.nejm.org/doi/full/10.1056/NEJM199501263320403 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7808487 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://www.ncbi.nlm.nih.gov/pubmed/24065243 PubMed] | + | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22959335 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://www.ncbi.nlm.nih.gov/pubmed/24065243 PubMed] | ||
==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}== | ==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}== | ||
Line 2,888: | Line 3,125: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3i|7+3i]], then Amsacrine & Cytarabine | *[[#7.2B3i|7+3i]], then Amsacrine & Cytarabine | ||
+ | |||
====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 | ||
===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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21951683 PubMed] | ||
==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}== | ==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}== | ||
Line 2,903: | Line 3,144: | ||
===Variant #1 {{#subobject:be3609|Variant=1}}=== | ===Variant #1 {{#subobject:be3609|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 20%"|Study | + | ! style="width: 20%" |Study |
− | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 20%"|Comparator | + | ! style="width: 20%" |Comparator |
− | !style="width: 20%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
− | !style="width: 20%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] |
|- | |- | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext Bornhäuser et al. 2012] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext Bornhäuser et al. 2012] | ||
Line 2,929: | Line 3,170: | ||
===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. [http://jco.ascopubs.org/content/28/17/2859.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439626 PubMed] | + | |
− | # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22959335 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. [http://jco.ascopubs.org/content/28/17/2859.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439626 PubMed] |
+ | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70349-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22959335 PubMed] | ||
==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}== | ==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}== | ||
Line 2,949: | Line 3,191: | ||
===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. [http://jco.ascopubs.org/content/33/35/4167.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26527780 PubMed] | + | |
+ | #'''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. [http://jco.ascopubs.org/content/33/35/4167.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26527780 PubMed] | ||
==HAM {{#subobject:1da5a5|Regimen=1}}== | ==HAM {{#subobject:1da5a5|Regimen=1}}== | ||
Line 2,971: | Line 3,214: | ||
|} | |} | ||
====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 | *PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus DAF | ||
====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 | ||
+ | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#HiDAC|HiDAC consolidation]] | *[[#HiDAC|HiDAC consolidation]] | ||
===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://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed] | + | #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://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed] | ||
==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}== | ==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}== | ||
Line 3,003: | Line 3,251: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#ICL|7+3i & Lomustine]] | *[[#ICL|7+3i & Lomustine]] | ||
+ | |||
====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>) | ||
====Hormonotherapy, reinduction==== | ====Hormonotherapy, reinduction==== | ||
+ | |||
*[[Norethandrolone (Nilevar)]] as follows: | *[[Norethandrolone (Nilevar)]] as follows: | ||
**If less than 60 kg: 10 mg PO once per day | **If less than 60 kg: 10 mg PO once per day | ||
Line 3,015: | Line 3,267: | ||
'''3-month cycle for 6 cycles, alternating with maintenance''' | '''3-month cycle for 6 cycles, alternating with maintenance''' | ||
====Chemotherapy, maintenance==== | ====Chemotherapy, maintenance==== | ||
+ | |||
*[[Methotrexate (MTX)]] as follows: | *[[Methotrexate (MTX)]] as follows: | ||
**If less than 60 kg: 20 mg PO twice per week in weeks 1 & 2 | **If less than 60 kg: 20 mg PO twice per week in weeks 1 & 2 | ||
Line 3,023: | Line 3,276: | ||
====Hormonotherapy, maintenance==== | ====Hormonotherapy, maintenance==== | ||
+ | |||
*[[Norethandrolone (Nilevar)]] as follows: | *[[Norethandrolone (Nilevar)]] as follows: | ||
**If less than 60 kg: 10 mg PO once per day | **If less than 60 kg: 10 mg PO once per day | ||
Line 3,030: | Line 3,284: | ||
===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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.67.6213 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28129526 PubMed] | + | |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.67.6213 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28129526 PubMed] | ||
==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}== | ==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}== | ||
Line 3,050: | Line 3,305: | ||
===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. [http://jco.ascopubs.org/content/28/17/2859.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/28/17/2859.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439626 PubMed] | ||
=Maintenance after first-line therapy= | =Maintenance after first-line therapy= | ||
Line 3,070: | Line 3,326: | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*7+2d | *7+2d | ||
+ | |||
====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 | ||
Line 3,077: | Line 3,336: | ||
===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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20497178 PubMed] | ||
==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}== | ==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}== | ||
Line 3,096: | Line 3,356: | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Decitabine_monotherapy|Decitabine induction]] | *[[#Decitabine_monotherapy|Decitabine induction]] | ||
+ | |||
====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. | ||
Line 3,104: | Line 3,367: | ||
===References=== | ===References=== | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed] | + | |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed] | ||
==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}== | ==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}== | ||
Line 3,121: | Line 3,385: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin induction]], with clinical benefit | *[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin induction]], with clinical benefit | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[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 | ||
Line 3,129: | Line 3,396: | ||
===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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] | + | |
+ | #'''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. 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. [http://jco.ascopubs.org/content/34/9/972.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed] | ||
==LoDAC {{#subobject:4c65c8|Regimen=1}}== | ==LoDAC {{#subobject:4c65c8|Regimen=1}}== | ||
Line 3,153: | Line 3,421: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*HiDAC, then amsacrine induction | *HiDAC, then amsacrine induction | ||
+ | |||
====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 | ||
Line 3,160: | Line 3,431: | ||
===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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10942228 PubMed] | ||
==Observation== | ==Observation== | ||
Line 3,218: | Line 3,490: | ||
''No further antineoplastic treatment. Reported efficacy for CALGB 9720 is based on the 2008 update. Reported efficacy for HOVON 43 AML/SAKK 30/01 is based on the 2010 update.'' | ''No further antineoplastic treatment. Reported efficacy for CALGB 9720 is based on the 2008 update. Reported efficacy for HOVON 43 AML/SAKK 30/01 is based on the 2010 update.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*ECOG E5483: HiDAC, then amsacrine induction | *ECOG E5483: HiDAC, then amsacrine induction | ||
*HOVON 43 AML/SAKK 30/01: [[#IDAC|IDAC consolidation]] x 1 | *HOVON 43 AML/SAKK 30/01: [[#IDAC|IDAC consolidation]] x 1 | ||
*SWOG S0106: [[#HiDAC|HiDAC consolidation]] x 3 | *SWOG S0106: [[#HiDAC|HiDAC consolidation]] x 3 | ||
+ | |||
===References=== | ===References=== | ||
− | # Sauter C, Berchtold W, Fopp M, Gratwohl A, Imbach P, Maurice P, Tschopp L, von Fliedner V, Cavalli F. Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival. Lancet. 1984 Feb 18;1(8373):379-82. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90424-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6141436 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10942228 PubMed] | + | #Sauter C, Berchtold W, Fopp M, Gratwohl A, Imbach P, Maurice P, Tschopp L, von Fliedner V, Cavalli F. Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival. Lancet. 1984 Feb 18;1(8373):379-82. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90424-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6141436 PubMed] |
− | # '''HOVON/SAKK AML4:''' Breems DA, Boogaerts MA, Dekker AW, Van Putten WL, Sonneveld P, Huijgens PC, Van der Lelie J, Vellenga E, Gratwohl A, Verhoef GE, Verdonck LF, Löwenberg B. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005 Jan;128(1):59-65. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2004.05282.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15606550 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10942228 PubMed] |
− | # Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, Hogge DE, Nilsson B, Or R, Romero AI, Rowe JM, Simonsson B, Spearing R, Stadtmauer EA, Szer J, Wallhult E, Hellstrand K. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial. Blood. 2006 Jul 1;108(1):88-96. Epub 2006 Mar 23. [http://www.bloodjournal.org/content/108/1/88.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16556892 PubMed] | + | #'''HOVON/SAKK AML4:''' Breems DA, Boogaerts MA, Dekker AW, Van Putten WL, Sonneveld P, Huijgens PC, Van der Lelie J, Vellenga E, Gratwohl A, Verhoef GE, Verdonck LF, Löwenberg B. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005 Jan;128(1):59-65. [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2004.05282.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15606550 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. [http://www.bloodjournal.org/content/100/4/1224.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149202 PubMed] | + | #Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, Hogge DE, Nilsson B, Or R, Romero AI, Rowe JM, Simonsson B, Spearing R, Stadtmauer EA, Szer J, Wallhult E, Hellstrand K. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial. Blood. 2006 Jul 1;108(1):88-96. Epub 2006 Mar 23. [http://www.bloodjournal.org/content/108/1/88.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16556892 PubMed] |
− | ## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0472 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652081/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18591543 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. [http://www.bloodjournal.org/content/100/4/1224.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149202 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 PubMed] | + | ##'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0472 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652081/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18591543 PubMed] |
− | ## '''Update:''' Löwenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, Ferrant A, Sonneveld P, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Breems D, de Muijnck H, Schaafsma R, Verhoef G, Döhner H, Gratwohl A, Pabst T, Ossenkoppele GJ, Maertens J; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); German Austrian AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010 Apr 1;115(13):2586-91. Epub 2010 Jan 26. [http://www.bloodjournal.org/content/115/13/2586.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20103782 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 PubMed] | + | ##'''Update:''' Löwenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, Ferrant A, Sonneveld P, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Breems D, de Muijnck H, Schaafsma R, Verhoef G, Döhner H, Gratwohl A, Pabst T, Ossenkoppele GJ, Maertens J; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); German Austrian AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010 Apr 1;115(13):2586-91. Epub 2010 Jan 26. [http://www.bloodjournal.org/content/115/13/2586.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20103782 PubMed] |
− | # '''CALGB 19808:''' Kolitz JE, George SL, Benson DM Jr, Maharry K, Marcucci G, Vij R, Powell BL, Allen SL, Deangelo DJ, Shea TC, Stock W, Bakan CE, Hars V, Hoke E, Bloomfield CD, Caligiuri MA, Larson RA; Alliance for Clinical Trials in Oncology. Recombinant interleukin-2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: results from Cancer and Leukemia Group B 19808. Cancer. 2014 Apr 1;120(7):1010-7. Epub 2013 Dec 31. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28516 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139069/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24382782 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://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23591789 PubMed] |
+ | #'''CALGB 19808:''' Kolitz JE, George SL, Benson DM Jr, Maharry K, Marcucci G, Vij R, Powell BL, Allen SL, Deangelo DJ, Shea TC, Stock W, Bakan CE, Hars V, Hoke E, Bloomfield CD, Caligiuri MA, Larson RA; Alliance for Clinical Trials in Oncology. Recombinant interleukin-2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: results from Cancer and Leukemia Group B 19808. Cancer. 2014 Apr 1;120(7):1010-7. Epub 2013 Dec 31. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28516 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139069/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24382782 PubMed] | ||
==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== | ==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== | ||
Line 3,250: | Line 3,525: | ||
''Note: This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ''Note: This trial should not be confused for the one by the same name in Ph+ B-ALL.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib consolidation]] | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib consolidation]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | + | |
+ | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | ||
'''Up to one year of sorafenib therapy, including consolidation course(s)''' | '''Up to one year of sorafenib therapy, including consolidation course(s)''' | ||
Line 3,258: | Line 3,536: | ||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | # 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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | + | #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. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 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://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed] | ||
=Relapsed or refractory, salvage therapy= | =Relapsed or refractory, salvage therapy= | ||
Line 3,278: | Line 3,557: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]] | *[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]] | ||
====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 | ||
Line 3,287: | Line 3,568: | ||
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 PubMed] | + | |
+ | #'''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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 PubMed] | ||
==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}== | ==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}== | ||
Line 3,311: | Line 3,593: | ||
====Chemotherapy, Course 1==== | ====Chemotherapy, Course 1==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (20 total doses) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (20 total doses) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push 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 |
====Chemotherapy, Course 2==== | ====Chemotherapy, Course 2==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 8 (16 total doses) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 8 (16 total doses) | ||
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push once per day on days 1, 3, 5 | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push once per day on days 1, 3, 5 | ||
Line 3,321: | Line 3,605: | ||
===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://www.ncbi.nlm.nih.gov/pubmed/16484584 PubMed] | + | |
+ | #'''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://www.ncbi.nlm.nih.gov/pubmed/16484584 PubMed] | ||
==CLAG {{#subobject:702383|Regimen=1}}== | ==CLAG {{#subobject:702383|Regimen=1}}== | ||
Line 3,340: | Line 3,625: | ||
|} | |} | ||
====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''' | ||
Line 3,345: | Line 3,631: | ||
===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://www.tandfonline.com/doi/full/10.3109/10428190009053545 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/19717379 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://www.tandfonline.com/doi/full/10.3109/10428190009053545 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed] | ||
==CLAG-M {{#subobject:51b417|Regimen=1}}== | ==CLAG-M {{#subobject:51b417|Regimen=1}}== | ||
Line 3,364: | Line 3,651: | ||
|} | |} | ||
====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''' | ||
Line 3,373: | Line 3,661: | ||
'''One course''' | '''One course''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients with PR were recommended to undergo a second course of CLAG-M. | *Patients with PR were recommended to undergo a second course of 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]] | ||
Line 3,378: | Line 3,667: | ||
===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://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed] | + | #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://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed] | ||
==CLARA {{#subobject:48978a|Regimen=1}}== | ==CLARA {{#subobject:48978a|Regimen=1}}== | ||
Line 3,398: | Line 3,688: | ||
|} | |} | ||
====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''' | ||
Line 3,404: | Line 3,695: | ||
'''One course with one re-induction allowed for patients with greater than 5% blasts at day 21''' | '''One course with one re-induction allowed for patients with greater than 5% blasts at day 21''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Patients achieving CR could receive consolidation with clofarabine reduced to 20 mg/m<sup>2</sup>, and cytarabine reduced to 1000 mg/m<sup>2</sup>, up to 2 cycles | *Patients achieving CR could receive consolidation with clofarabine reduced to 20 mg/m<sup>2</sup>, and cytarabine reduced to 1000 mg/m<sup>2</sup>, up to 2 cycles | ||
===References=== | ===References=== | ||
− | # 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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08831.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21848522 PubMed] | + | |
+ | #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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08831.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21848522 PubMed] | ||
==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}== | ==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}== | ||
Line 3,425: | Line 3,718: | ||
''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.'' | ''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==== | ====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)]] as follows (per physician choice): | *[[Cytarabine (Ara-C)]] as follows (per physician choice): | ||
Line 3,442: | Line 3,736: | ||
|} | |} | ||
====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 | ||
Line 3,447: | Line 3,742: | ||
'''At least one cycle''' | '''At least one cycle''' | ||
====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]] | ||
Line 3,473: | Line 3,769: | ||
|} | |} | ||
====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 | ||
Line 3,478: | Line 3,775: | ||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*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 3,490: | Line 3,788: | ||
*Parenteral nutrition allowed | *Parenteral nutrition allowed | ||
*No routine use of growth factors | *No routine use of growth factors | ||
+ | |||
'''1 to 4 cycles''' | '''1 to 4 cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*See individual papers for details | *See individual papers for details | ||
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15486072 PubMed] | + | |
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21273514 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15486072 PubMed] |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21273514 PubMed] | ||
<!-- Presented in part at the 53rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and at the 16th Congress of the European Hematology Association, London, United Kingdom, June 9-12, 2011. --> | <!-- Presented in part at the 53rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and at the 16th Congress of the European Hematology Association, London, United Kingdom, June 9-12, 2011. --> | ||
− | # '''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. [http://jco.ascopubs.org/content/30/20/2492.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585697 PubMed] | + | #'''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. [http://jco.ascopubs.org/content/30/20/2492.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585697 PubMed] |
− | # 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://onlinelibrary.wiley.com/doi/10.1111/bjh.13437/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25854284 PubMed] | + | #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://onlinelibrary.wiley.com/doi/10.1111/bjh.13437/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26283567 PubMed] |
==Cytarabine & Mitoxantrone {{#subobject:fba448|Regimen=1}}== | ==Cytarabine & Mitoxantrone {{#subobject:fba448|Regimen=1}}== | ||
Line 3,518: | Line 3,819: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (12 total doses) | *[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (12 total doses) | ||
*[[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 | ||
Line 3,537: | Line 3,839: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once every 12 hours on days 1 to 5 (10 total doses) | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once every 12 hours on days 1 to 5 (10 total doses) | ||
*[[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 | ||
Line 3,542: | Line 3,845: | ||
'''One course''' | '''One course''' | ||
===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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0142%2820000501%2988:9%3C2037::AID-CNCR8%3E3.0.CO;2-K/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10813714 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0142%2820000501%2988:9%3C2037::AID-CNCR8%3E3.0.CO;2-K/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10813714 PubMed] | ||
==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}== | ==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}== | ||
Line 3,552: | Line 3,856: | ||
===Regimen {{#subobject:7683cc|Variant=1}}=== | ===Regimen {{#subobject:7683cc|Variant=1}}=== | ||
{| class="wikitable" style="width: 75%; text-align:center;" | {| class="wikitable" style="width: 75%; text-align:center;" | ||
− | !style="width: 33%"|Study | + | ! style="width: 33%" |Study |
− | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
|- | |- | ||
|[http://jco.ascopubs.org/content/6/2/213.abstract Ho et al. 1988] | |[http://jco.ascopubs.org/content/6/2/213.abstract Ho et al. 1988] | ||
Line 3,562: | Line 3,866: | ||
|} | |} | ||
====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 | ||
===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. [http://jco.ascopubs.org/content/6/2/213.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/6/2/213.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3422260 PubMed] | ||
==FLAG {{#subobject:551761|Regimen=1}}== | ==FLAG {{#subobject:551761|Regimen=1}}== | ||
Line 3,584: | Line 3,890: | ||
|} | |} | ||
====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''' | ||
Line 3,594: | Line 3,901: | ||
===Variant #2, BSA-based G-CSF {{#subobject:bdc7e4|Variant=1}}=== | ===Variant #2, BSA-based G-CSF {{#subobject:bdc7e4|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Comparative Efficacy]] |
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)] | ||
Line 3,607: | Line 3,914: | ||
''Note: this regimen was studied in patients up to 21 years of age.'' | ''Note: this regimen was studied in patients up to 21 years of age.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given third, 4 hours after the start of fludarabine''' | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given third, 4 hours after the start of fludarabine''' | ||
Line 3,613: | Line 3,921: | ||
'''Two cycles''' | '''Two cycles''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]] | *[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]] | ||
+ | |||
===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://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199806%2958:2%3C105::AID-AJH3%3E3.0.CO;2-W/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9625576 PubMed] | + | |
− | # '''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 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://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199806%2958:2%3C105::AID-AJH3%3E3.0.CO;2-W/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9625576 PubMed] |
+ | #'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed] | ||
==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}== | ==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}== | ||
Line 3,637: | Line 3,948: | ||
|} | |} | ||
====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''' | ||
Line 3,643: | Line 3,955: | ||
===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://www.ncbi.nlm.nih.gov/pubmed/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://link.springer.com/article/10.1007%2Fs00277-003-0624-2 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12707726 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://www.ncbi.nlm.nih.gov/pubmed/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://link.springer.com/article/10.1007%2Fs00277-003-0624-2 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12707726 PubMed] | ||
==F-SHAI {{#subobject:9e1c5f|Regimen=1}}== | ==F-SHAI {{#subobject:9e1c5f|Regimen=1}}== | ||
Line 3,667: | Line 3,980: | ||
|} | |} | ||
====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 | ||
Line 3,673: | Line 3,987: | ||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day from day 14 until ANC greater than 1500/uL | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day from day 14 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 | ||
Line 3,679: | Line 3,994: | ||
===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://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24150216 PubMed] | ||
==HiDAC {{#subobject:1dddf5|Regimen=1}}== | ==HiDAC {{#subobject:1dddf5|Regimen=1}}== | ||
Line 3,702: | Line 4,018: | ||
''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.'' | ||
====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>) | ||
Line 3,720: | Line 4,037: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 | ||
'''One course''' | '''One course''' | ||
===References=== | ===References=== | ||
− | # 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://www.sciencedirect.com/science/article/pii/S0145212699000879 link to SD article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19710500 PubMed] | + | #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://www.sciencedirect.com/science/article/pii/S0145212699000879 link to SD article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19710500 PubMed] | ||
==MEC {{#subobject:48e49b|Regimen=1}}== | ==MEC {{#subobject:48e49b|Regimen=1}}== | ||
Line 3,743: | Line 4,062: | ||
|} | |} | ||
====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 | ||
Line 3,763: | Line 4,083: | ||
|} | |} | ||
====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 | ||
Line 3,789: | Line 4,110: | ||
''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.'' | ||
====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''' | ||
Line 3,795: | Line 4,117: | ||
'''One course''' | '''One course''' | ||
===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. [http://jco.ascopubs.org/content/9/7/1210.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020609 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. [http://jco.ascopubs.org/content/9/7/1210.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2045861 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. [http://jco.ascopubs.org/content/23/18/4110.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15961759 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. [http://ascopubs.org/doi/full/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020609 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.28974/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25223583 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. [http://jco.ascopubs.org/content/23/18/4110.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15961759 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.28974/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25223583 PubMed] | ||
=Consolidation after salvage therapy= | =Consolidation after salvage therapy= | ||
Line 3,837: | Line 4,160: | ||
{{#lst:Allogeneic HSCT|334af6}} | {{#lst:Allogeneic HSCT|334af6}} | ||
===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://www.nejm.org/doi/full/10.1056/NEJM198312013092202 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6355849 PubMed] | + | |
− | # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26429297 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://www.nejm.org/doi/full/10.1056/NEJM198312013092202 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6355849 PubMed] |
− | # '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28380315 PubMed] | + | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26429297 PubMed] |
+ | #'''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28380315 PubMed] | ||
==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}== | ==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}== | ||
Line 3,891: | Line 4,215: | ||
{{#lst:Allogeneic HSCT|d415c}} | {{#lst:Allogeneic HSCT|d415c}} | ||
===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/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18489993 Pubmed] | + | |
− | # 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. [http://jco.ascopubs.org/content/31/6/701.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23129746 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/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18489993 Pubmed] |
− | # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26429297 PubMed] | + | #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. [http://jco.ascopubs.org/content/31/6/701.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23129746 PubMed] |
+ | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26429297 PubMed] | ||
==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}== | ==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}== | ||
Line 3,911: | Line 4,236: | ||
''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==== | ====Preceding treatment==== | ||
+ | |||
*[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine salvage]] | *[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine salvage]] | ||
{{#lst:Allogeneic HSCT|a408ed}} | {{#lst:Allogeneic HSCT|a408ed}} | ||
===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://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26283567 PubMed] | ||
==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}== | ==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}== | ||
Line 3,932: | Line 4,259: | ||
''Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".'' | ''Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]] | *[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4, every other week | *[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4, every other week | ||
*[[Thioguanine (Tabloid)]] 100 mg/m<sup>2</sup> PO once per day for up to 4 weeks maximum | *[[Thioguanine (Tabloid)]] 100 mg/m<sup>2</sup> PO once per day for up to 4 weeks maximum | ||
+ | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*Allogeneic HSCT | *Allogeneic HSCT | ||
+ | |||
===References=== | ===References=== | ||
− | # '''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed] | + | |
+ | #'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed] | ||
==CYVE {{#subobject:4bd791|Regimen=1}}== | ==CYVE {{#subobject:4bd791|Regimen=1}}== | ||
Line 3,958: | Line 4,292: | ||
''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.'' | ''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]] | *[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]] | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m<sup>2</sup>) | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days 1 to 4 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days 1 to 4 | ||
+ | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | |||
*[[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]] | *[[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]] | ||
+ | |||
===References=== | ===References=== | ||
− | # '''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed] | + | |
+ | #'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed] | ||
=Relapsed or refractory, subsequent lines of therapy= | =Relapsed or refractory, subsequent lines of therapy= | ||
Line 3,985: | Line 4,326: | ||
|} | |} | ||
====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 | ||
Line 3,991: | Line 4,333: | ||
===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 (GFM). 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://www.ncbi.nlm.nih.gov/pubmed/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 (GFM). 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://www.ncbi.nlm.nih.gov/pubmed/20664061 PubMed] | ||
==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}== | ==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}== | ||
Line 4,009: | Line 4,352: | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | |||
*[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day | *[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day | ||
Line 4,017: | Line 4,361: | ||
===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. --> | ||
− | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22422826 PubMed] | + | |
+ | #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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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. Review. [http://jco.ascopubs.org/content/8/5/813.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. Review. [http://jco.ascopubs.org/content/8/5/813.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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]. [http://jco.ascopubs.org/content/21/24/4642.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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]. [http://jco.ascopubs.org/content/21/24/4642.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14673054 PubMed] | ||
=Prognosis= | =Prognosis= | ||
Line 4,051: | Line 4,398: | ||
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%) | ||
Line 4,056: | Line 4,404: | ||
===References=== | ===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. [http://jco.ascopubs.org/content/23/9/1969.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/23/9/1969.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15632409 PubMed] | ||
==Prognosis in cytogenetically normal AML== | ==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. [https://www.nejm.org/doi/full/10.1056/NEJMoa074306 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJMoa074306 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18450602 PubMed] | ||
=Investigational agents= | =Investigational agents= | ||
''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.'' | ||
+ | |||
*[[Alvocidib (Flavopiridol)]] | *[[Alvocidib (Flavopiridol)]] | ||
*[[Vadastuximab talirine (SGN-CD33A)]] | *[[Vadastuximab talirine (SGN-CD33A)]] | ||
Line 4,072: | Line 4,423: | ||
==Antifungal prophylaxis== | ==Antifungal prophylaxis== | ||
− | # '''Review:''' Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015 Dec 24;126(26):2790-7. Epub 2015 Oct 26. [http://www.bloodjournal.org/content/126/26/2790.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26504183 PubMed] | + | |
+ | #'''Review:''' Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015 Dec 24;126(26):2790-7. Epub 2015 Oct 26. [http://www.bloodjournal.org/content/126/26/2790.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26504183 PubMed] | ||
[[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 02:27, 4 June 2019
Section editor | |
---|---|
Martin W. Schoen, MD, MPH Saint Louis University St. Louis, MO mwschoen |
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. If you still can't find it, please let us know so we can add it!
Note: biomarker-specific regimens have been moved to dedicated pages:
88 regimens on this page
144 variants on this page
|
Guidelines
ELN
Current
- 2017: Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel link to PMC article PubMed
Older
- 2010: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet PubMed
ESMO
- 2013: Fey et al. Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
"How I treat"
- 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
Upfront induction therapy, standard and older "fit" patients
These are aggressive remission induction regimens given with curative intent.
7+3d (standard-dose)
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7+3d: 7 days of cytarabine + 3 days of daunorubicin
AD: Ara-C (Cytarabine) & Daunorubicin
DA: Daunorubicin & Ara-C (Cytarabine)
Variant #1, 700/135 (CI Ara-C)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yates et al. 1973 | Non-randomized, <20 pts | ||
Rai et al. 1981 (CALGB 7421) | Phase III (E) | 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 | Phase III (E) | 1. AVML | Not directly compared |
2. TAD | Superior time to CR | ||
Yates et al. 1982 (CALGB 7721) | Phase III (C) | 1. 7+3d (low-dose) | Seems not superior |
2. 7+3a (30 mg/m2) | Seems not superior | ||
Vogler et al. 1984 | Non-randomized portion of RCT | ||
Preisler et al. 1987 (CALGB 7921) | Phase III (C) | 1. 10+3d | Seems not superior |
2. TAD | Seems not superior | ||
Stein et al. 1990 | Phase III (C) | MA | Seems not superior |
Arlin et al. 1990 | Phase III (C) | 7+3m | Seems not superior |
Dillman et al. 1991 (CALGB 8321) | Phase III (C) | 7+3d (higher-dose Ara-C) | Seems not superior |
Wiernik et al. 1992 | Phase III (C) | 7+3i | Seems to have inferior OS |
Vogler et al. 1992 | Phase III (C) | 7+3i | Seems to have inferior CR rate |
Rowe et al. 2004 (ECOG E3993) | Phase III (C) | 1. 7+3d + GM-CSF 2. 7+3i 3. 7+3i + GM-CSF 4. 7+3m 5. 7+3m + GM-CSF |
Seems not superior |
Latagliata et al. 2008 (GIMEMA GSI 103 AMLE) | Phase III (C) | 7+3 (Daunoxome) | Seems not superior |
Fernandez et al. 2009 (ECOG E1900) | Phase III (C) | 7+3d (high-dose) | Inferior OS |
Dombret et al. 2015 (AZA-AML-001) | Phase III (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
Variant #2, 700/150 (CI Ara-C)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bishop et al. 1990 | Phase III (C) | ADE | Seems not superior |
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
Variant #3, 1120/120 (intermittent Ara-C)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Masaoka et al. 1996 | Randomized Phase II (E) | 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
Variant #4, 1400/135 (CI Ara-C)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Dillman et al. 1991 (CALGB 8321) | Phase III (E) | 7+3d (lower-dose Ara-C) | Seems not superior |
Weick et al. 1996 | Phase III (C) | HDAC+3d | Seems not superior |
Anderson et al. 2002 (SWOG S9333) | Phase III (C) | ME | Seems not superior |
Moore et al. 2004 (CALGB 9222) | Non-randomized portion of RCT | ||
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | Phase III (C) | 7+3d (high-dose) | Inferior CR rate |
Lee et al. 2011 (ADcomparison) | Phase III (C) | 7+3d (high-dose) | Seems to have inferior OS |
Hengeveld et al. 2012 (AML 8B) | Non-randomized portion of RCT | ||
Stone et al. 2015 (ACCEDE) | Phase III (C) | Amonafide & Cytarabine | Seems not superior |
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 verified protocol 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 verified protocol 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 verified protocol PubMed
- Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L. 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 verified protocol PubMed
- Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A. 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 SD 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 protocol 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 verified protocol 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 verified protocol PubMed
- Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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 protocol 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 protocol PubMed
- Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. 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 protocol 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 protocol 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 verified protocol 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 verified protocol 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 verified protocol 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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 protocol PubMed
- AML 8B: 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. 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 Organization 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 protocol 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 verified protocol PubMed
- 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 verified protocol 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. link to original article link to PMC article PubMed
7+3d (intermediate-dose)
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7+3d: 7 days of cytarabine + 3 days of daunorubicin
Variant #1, CI Ara-C (100 mg/m2)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schaich et al. 2013 (AML2003) | Non-randomized portion of RCT | ||
Serve et al. 2013 | Randomized Phase II (C) | 7+3d & Sorafenib | Seems not superior |
Petersdorf et al. 2013 (SWOG S0106) | Phase III (C) | 7+3d & GO | Seems not superior |
Müller-Tidow et al. 2015 (AML-AZA) | Phase III (C) | 7+3d & Azacitidine | Seems not superior |
Dombret et al. 2015 (AZA-AML-001) | Phase III (C) | Azacitidine | Might have inferior OS |
Röllig et al. 2015 (SORAML) | Randomized Phase II (C) | 7+3d & Sorafenib | Seems to have inferior EFS |
Lancet et al. 2018 (CLTR0310-301) | Phase III (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
- SWOG S0106: HiDAC consolidation x 3
- CLTR0310-301: 5+2d consolidation
Variant #2, CI Ara-C (200 mg/m2)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Holowiecki et al. 2004 (PALG AML1/1999) | Phase III (C) | DAC | Inferior CR rate after first induction |
Chevallier et al. 2010 (LAM-2001) | Phase III (C) | 7+5i | Seems not superior |
Holowiecki et al. 2012 (PALG AML1/2004) | Phase III (C) | 1. DAC | Inferior OS |
2. DAF | Seems to have inferior OS | ||
Castaigne et al. 2012 (ALFA-0701) | Phase III (C) | 7+3d & GO | Inferior EFS |
Stone et al. 2017 (RATIFY) | Phase III (C) | 7+3d & Midostaurin | Inferior OS |
Note: patients in RATIFY had FLT3+ disease.
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 medications
- "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 (PALG). 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 verified protocol 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 protocol 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 verified protocol 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 verified protocol 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. link to original article link to PMC article PubMed
- 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 verified protocol PubMed
- 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 protocol 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
- 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 verified protocol 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. 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 verified protocol 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 PubMed
- RATIFY: Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. link to original article link to PMC article contains verified protocol PubMed
- 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 protocol PubMed
7+3d (high-dose)
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7+3d: 7 days of cytarabine + 3 days of daunorubicin
Variant #1, 700/270
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fernandez et al. 2009 (ECOG E1900) | Phase III (E) | 7+3d (standard-dose) | Superior OS |
Zeidner et al. 2015 (JHOC-J1101) | Randomized Phase II (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
Variant #2, 1400/240
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Castaigne et al. 2004 (ALFA 9000) | Phase III (C) | 1. 7+3d x 2 2. Timed sequential induction |
Seems not superior |
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
Variant #3, 1400/270
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | Phase III (E) | 7+3d (standard-dose) | Superior CR rate |
Lee et al. 2011 (ADcomparison) | Phase III (E) | 7+3d (standard-dose) | Seems to have superior OS |
Lee et al. 2017 (COSAH C-022) | Phase III (C) | 7+3i | Seems not superior |
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: HiDAC consolidation if good- or intermediate-risk cytogenetics, or cytarabine & etoposide consolidation if high-risk cytogenetics.
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 verified protocol 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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 protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol PubMed
7+3d & GO
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7+3d & GO: 7 days of Cytarabine, 3 days of daunorubicin, Gemtuzumab Ozogamicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Castaigne et al. 2012 (ALFA-0701) | Phase III (E) | 7+3d (intermediate-dose) | Superior 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 once per day on days 1 to 3
- 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
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 verified protocol 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. link to original article link to PMC article PubMed
7+3i
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7+3i: 7 days of cytarabine + 3 days of idarubicin
AI: Ara-C (Cytarabine) & Idarubicin
IA: Idarubicin & Ara-C (Cytarabine)
Variant #1, 80/12, intermittent Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Masaoka et al. 1996 | Randomized Phase II (E) | 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
Variant #2, 100/12, CI Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Vogler et al. 1992 | Phase III (E) | 7+3d | Seems to have superior CR rate |
Haas et al. 1993 | Non-randomized | ||
Rowe et al. 2004 (ECOG E3993) | Phase III (E) | 1. 7+3d (standard-dose) 2. 7+3d + GM-CSF 3. 7+3i + GM-CSF 4. 7+3m 5. 7+3m + GM-CSF |
Seems not superior |
Miyawaki et al. 2005 (JALSG AML97) | Non-randomized portion of RCT | ||
Ohtake et al. 2010 (JALSG AML95) | Phase III (C) | Individualized chemotherapy | Seems not superior |
Ohtake et al. 2010 (JALSG AML201) | Phase III (C) | 7+5d | Seems not superior |
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
Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.
Variant #3, 100/13, CI Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wiernik et al. 1992 | Phase III (E) | 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
Variant #4, 200/12, CI Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Löwenberg et al. 2003 (HOVON/SAKK AML 29) | Phase III (C) | 7+3i & G-CSF | Seems to have inferior DFS |
Pautas et al. 2010 (ALFA-9801) | Phase III (C) | 1. 7+3d (high-dose) 2. 7+4i |
Seems not superior |
Löwenberg et al. 2011 (HOVON/SAKK AML 42) | Phase III (C) | HDAC+3i | Seems not superior |
Löwenberg et al. 2017 (HOVON-102) | Phase III (C) | 7+3i & Clofarabine | Seems not superior |
Lee et al. 2017 (COSAH C-022) | Phase III (C) | 7+3d (high-dose) | Seems not superior |
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
Variant #5, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Dombret et al. 2015 (AZA-AML-001) | Phase III (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
- 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 verified protocol PubMed
- Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL. 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 protocol 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 protocol 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 verified protocol 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 verified protocol PubMed
- 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 AML 97 Study. 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 protocol 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 verified protocol PubMed
- 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 protocol 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
- 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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. link to original article contains verified protocol PubMed
- 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 protocol link to PMC article 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. link to original article link to PMC article PubMed
- 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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (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 verified protocol PubMed
- 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 verified protocol PubMed
7+3i & Sorafenib
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Regimen
Study | Evidence |
---|---|
Ravandi et al. 2010AML | Phase I/II |
Note: Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.
Chemotherapy
- Cytarabine (Ara-C) 1500 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m2)
- Patients older than 60 received: 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
- Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 7
7-day course
Subsequent treatment
References
- 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 verified protocol link to PMC article 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. link to original article link to PMC article PubMed
7+3d & Glasdegib
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Regimen
Study | Evidence |
---|---|
Cortes et al. 2018 | Phase II |
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
- Glasdegib (Daurismo)100 mg PO Qday for 28 days, started on day -3 for 6 cycles
28-day course
Subsequent treatment
References
- 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 verified protocol link to PMC article PubMed
7+3m
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7+3m: 7 days of cytarabine + 3 days of mitoxantrone
MAC: Mitoxantrone & Ara-C (Cytarabine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rowe et al. 2004 (ECOG E3993) | Phase III (E) | 1. 7+3d (standard-dose) 2. 7+3d + GM-CSF 3. 7+3i 4. 7+3i + GM-CSF 5. 7+3m + GM-CSF |
Seems not superior |
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
- 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 verified protocol PubMed
ADE (standard-dose Ara-C)
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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
Variant #1, 7-3-3, 700/180/300
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baer et al. 2002 (CALGB 9720) | Phase III (C) | ADEP | Seems not superior |
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
One course
Variant #2, 7-3-7, 700/150/525
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bishop et al. 1996 | Phase III (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
Variant #3, 8-3-5, 1600/150/500, intermittent Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hann et al. 1997 (UK MRC AML10) | Phase III (E) | DAT 3+8 | Seems not superior |
Burnett et al. 2010 (UK MRC AML15) | Phase III (C) | See note | See note |
Gamis et al. 2014 (COG AAML0531) | Phase III (C) | See note | See note |
Note: these trials have complicated treatment schemas; see papers for details.
Preceding treatment
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
- Other trials: Consolidation (see paper for details)
Variant #4, 10-3-5, 1000/150/250, CI Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Willemze et al. 2013 (EORTC-GIMEMA AML-12) | Phase III (C) | ADE (high-dose Ara-C) | Might 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
Variant #5, 10-3-5, 1025/150/500, CI Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mandelli et al. 2009 (EORTC-GIMEMA AML-10) | Phase III (C) | 1. AIE 2. AME |
Seems not superior |
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
Variant #6, 10-3-5, 2000/150/500, intermittent Ara-C
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hann et al. 1997 (UK MRC AML10) | Phase III (E) | DAT 3+10 | Seems not superior |
Burnett et al. 1999 (UK MRC AML12) | Phase III (C) | See note | See note |
Burnett et al. 2010 (UK MRC AML15) | Phase III (C) | See note | See note |
Gamis et al. 2014 (COG AAML0531) | Phase III (C) | See note | See note |
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
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 protocol 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 verified protocol 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
- 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 protocol PubMed
- 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. 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
- 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
- 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 verified protocol PubMed
- COG AAML0531: Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article contains verified protocol PubMed
ADE (high-dose Ara-C)
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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
Variant #1, HIDAC-3-5
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Willemze et al. 2013 (EORTC-GIMEMA AML-12) | Phase III (E) | ADE (standard-dose Ara-C) | Might have superior OS |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5, 7 (8 doses per cycle)
- 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
Variant #2, HIDAC-3-7
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bishop et al. 1996 | Phase III (E) | ADE (standard-dose Ara-C) | Superior DFS |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on days 1, 3, 5, 7 (8 doses per cycle)
- 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 protocol 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 verified protocol PubMed
CIA
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CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)
Variant #1, 15/10/1000
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Jabbour et al. 2017 | Randomized Phase II (E) | FIA | Seems not superior |
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
One course
Subsequent treatment
- Patients not achieving CR or CRp could undergo a second induction
- Patients achieving CR or CRp: CIA consolidation
Variant #2, 20/10/1000
Study | Evidence |
---|---|
Nazha et al. 2013 | Phase II |
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 medications
- 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. link to PMC article contains verified protocol PubMed
- 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 verified protocol PubMed
DA 3 + 10, GO
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DA 3 + 10, GO: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine, Gemtuzumab Ozogamicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burnett et al. 2010 (UK MRC AML15) | Phase III (E) | See note | See note |
Burnett et al. 2012 (UK NCRI AML16) | Phase III (E) | DA 3 + 10 | Seems to have superior OS |
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
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 1
One 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 contains verified protocol 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 verified protocol 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. link to original article contains verified protocol 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
DA 3 + 10
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DA 3 + 10: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine
Variant #1, 50 mg/m2 dauno
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burnett et al. 2010 (UK MRC AML15) | Phase III (C) | See note | See note |
Burnett et al. 2012 (UK NCRI AML16) | Phase III (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
One course
Subsequent treatment
- See papers for details (to be completed).
Variant #2, 60 mg/m2 dauno
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burnett et al. 2015 (UK NCRI AML17) | Phase III (C) | DA 3 + 10 (high-dose) | Seems not superior |
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
One course
Subsequent treatment
- Complex randomization; 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
- 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 verified protocol 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. link to original article contains verified protocol 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 verified protocol link to PMC article PubMed
DAC
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DAC: Daunorubicin, Ara-C (Cytarabine), Cladribine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Holowiecki et al. 2004 (PALG AML1/1999) | Phase III (E) | DA | Superior CR rate after first induction |
Holowiecki et al. 2012 (PALG AML1/2004) | Phase III (E) | 1. DA | Superior OS |
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 medications
- "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 studies underwent a second course with the same drugs, doses, and schedule.
- Non-responders in PALG AML1/1999: CLAG salvage
- Patients in remission in both studies: HAM, then HiDAC 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 (PALG). 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 verified protocol 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 verified protocol PubMed
FLAG-Ida
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FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Lenograstim), Idarubicin
Regimen
Study | Evidence |
---|---|
Burnett et al. 2010 (UK MRC AML15) | Phase III (*) |
This trial has a complex randomization; to be completed.
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
- Lenograstim (Granocyte) 263 mcg SC once per day on days 1 to 7
- Idarubicin (Idamycin) 8 mg/m2 IV once per day on days 4 to 6
One 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
- 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
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HAA: Homoharringtonine (Omacetaxine), Ara-C (Cytarabine), Aclarubicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jin et al. 2013 | Phase III (E) | 1. DA | Superior EFS |
2. HAD | Not reported |
Unlikely to be completed since there were significantly more deaths in this arm, despite a superior primary efficacy endpoint.
Chemotherapy
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 PubMed
HAD
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HAD: Homoharringtonine (Omacetaxine), Ara-C (Cytarabine), Daunorubicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jin et al. 2013 | Phase III (E) | 1. DA | Might have superior EFS |
2. HAA | Not reported |
Unlikely to be completed since there were significantly more deaths in this arm, despite a trend towards a superior primary efficacy endpoint.
Chemotherapy
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 PubMed
ICE (Idarubicin)
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ICE: Idarubicin, Cytarabine, Etoposide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bradstock et al. 2004 (ALLG M7) | Non-randomized portion of RCT | ||
Schlenk et al. 2004 | Phase III (C) | A-ICE | Inferior OS |
Russo et al. 2005 | Phase III (C) | FLAI | Inferior CR rate |
Entz-Werle et al. 2005 | Phase III (C) | MCE | Seems not superior |
de Witte et al. 2010 (CRIANT) | Non-randomized portion of RCT | ||
Bassan et al. 2019 (NILG AML 02/06) | Phase III (C) | sHD | Seems not superior |
Chemotherapy
- Idarubicin (Idamycin) 12 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Cytarabine (Ara-C) 100 mg/m2 IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m2)
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
One 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
- EORTC 58921: Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; EORTC Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. 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
- 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 verified protocol PubMed
ICL
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ICL: Idarubicin, Cytarabine, Lomustine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pigneux et al. 2017 (LAM-SA 2007) | Phase III (E) | IA | Superior OS |
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
One 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 verified protocol PubMed
MEC
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MEC: Mitoxantrone, Etoposide, Cytarabine
MICE: MItoxantrone, Cytarabine, Etoposide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jehn et al. 2006 (EORTC/GIMEMA AML-13) | Non-randomized portion of RCT | ||
Amadori et al. 2013 (EORTC/GIMEMA AML-17) | Phase III (C) | GO, then MICE | Might have superior OS |
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)
One course
References
- EORTC/GIMEMA AML-13: 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 verified protocol 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
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fenaux et al. 2009 (AZA PH GL 2003) | Phase III (E) | Investigator's choice of: 1. Best supportive care 2. LoDAC 3. Intensive chemotherapy |
Superior OS |
Dombret et al. 2015 (AZA-AML-001) | Phase III (E) | 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 |
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
- 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 verified protocol link to PMC article 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. link to original article link to PMC article PubMed
Azacitidine & Venetoclax
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Regimen
Study | Evidence |
---|---|
DiNardo et al. 2018 (M14-358) | Phase Ib, >20 pts |
Patients with WBC greater than 25 x 109/L at presentation were pre-treated with hydroxyurea or leukapheresis.
Chemotherapy, induction
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
- Venetoclax (Venclexta) 400, 800, or 1200 mg PO once per day
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 verified protocol 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. 2018 Oct 25. [Epub ahead of print] link to original article PubMed
Azacitidine & Gemtuzumab ozogamicin
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Regimen
Study | Evidence |
---|---|
Nand et al. 2008 | Phase II |
Nand et al. 2013 (SWOG S0703) | Phase II |
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 medications, 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
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 8
Supportive medications
- "Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)
One cycle
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 verified protocol 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 verified protocol link to PMC article PubMed
Best supportive care
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Löwenberg et al. 1989 | Phase III (C) | Cytarabine, Daunorubicin, Vincristine | Seems to have inferior OS |
Harousseau et al. 2009 (FIGHT-AML-301) | Phase III (C) | Tipifarnib | Seems not superior |
Kantarjian et al. 2012 (DACO-016) | Phase III (C) | Decitabine | Might have inferior OS |
Dombret et al. 2015 (AZA-AML-001) | Phase III (C) | Azacitidine | Might have inferior OS |
Amadori et al. 2016 (EORTC/GIMEMA AML-19) | Phase III (C) | Gemtuzumab ozogamicin | Inferior OS |
No active antineoplastic treatment, although some trials consider Hydroxyurea (Hydrea) to be a component of best supportive care.
References
- Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, Cauchie C, Peetermans M, Solbu G, Suciu S, Stryckmans P. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989 Sep;7(9):1268-74. link to original article PubMed
- FIGHT-AML-301: Harousseau JL, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, Ossenkoppele GJ, Alexeeva JA, Beutel G, Maertens J, Vidriales MB, Dombret H, Thomas X, Burnett AK, Robak T, Khuageva NK, Golenkov AK, Tothova E, Mollgard L, Park YC, Bessems A, De Porre P, Howes AJ; FIGHT-AML-301 Investigators. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009 Aug 6;114(6):1166-73. Epub 2009 May 21. link to original article PubMed
- 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 verified protocol link to PMC article 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. link to original article PubMed
- 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 verified protocol link to PMC article 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. link to original article link to PMC article PubMed
- 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. 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 PubMed
Clofarabine monotherapy
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Variant #1, 20 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burnett et al. 2012 (UK NCRI AML16) | Phase III (E) | LoDAC | Seems not superior (*) |
Note: reported 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
Variant #2, 30 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Faderl et al. 2008 | Randomized Phase II (E) | Clofarabine & LoDAC | Seems to have inferior EFS |
Burnett et al. 2010 (UWCM-001 and BIOV-121) | Phase II |
Chemotherapy
- Clofarabine (Clolar) 30 mg/m2 IV over 60 minutes once per day on days 1 to 5
One course
Subsequent treatment
- A second induction was permitted for SD or better.
- Faderl et al. 2008: Responders proceeded to clofarabine & cytarabine consolidation
References
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol 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. link to original article contains verified protocol 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
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Clofarabine & LoDAC: Clofarabine & Low Dose Ara-C (Cytarabine)
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Faderl et al. 2008 | Randomized Phase II (E) | 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
One course
Subsequent treatment
- A second induction was permitted for SD or better
- Responders proceeded to clofarabine & cytarabine consolidation
Variant #2
Study | Evidence |
---|---|
Faderl et al. 2010 | Phase II |
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
One course
Subsequent treatment
- Patients not achieving CR could undergo an identical second induction after at least 28 days.
- Patients not achieving CR after the second induction were given salvage decitabine
- Patients achieving CR: Clofarabine & low-dose cytarabine alternating with decitabine consolidation
References
- 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 verified protocol link to PMC article 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. 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
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CPX-351: Liposomal Cytarabine and Daunorubicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lancet et al. 2014 (CLTR0308-204) | Randomized Phase II (E) | 7+3d (intermediate-dose) | Might have superior ORR |
Lancet et al. 2018 (CLTR0310-301) | Phase III (E) | 7+3d (intermediate-dose) | Superior OS |
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
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
- 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 protocol PubMed
Decitabine monotherapy
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Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Issa et al. 2014 | Randomized Phase II (C) | Decitabine & Valproate | Seems not superior |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
4- to 6-week cycles
Variant #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kantarjian et al. 2012 (DACO-016) | Phase III (E) | 1. LoDAC 2. Best supportive care |
Might have superior OS |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
Supportive medications
- Hydroxyurea (Hydrea) (dose not specified) could be used up until cycle 1 day 15
28-day cycles
Variant #3
Study | Evidence |
---|---|
Blum et al. 2010 | Phase II |
Welch et al. 2016 | Phase II |
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 10
Supportive medications
- Hydroxyurea (Hydrea) (dose not specified) allowed during and prior to cycle 1
28-day cycles
Subsequent treatment
- Blum et al. 2010, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above
- Blum et al. 2010, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by decitabine maintenance
References
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol link to PMC article 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. 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 verified protocol link to PMC article PubMed
- 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 verified protocol link to PMC article PubMed
Decitabine & Venetoclax
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Variant #1, 5 days of decitabine
Study | Evidence |
---|---|
DiNardo et al. 2018 (M14-358) | Phase Ib, >20 pts |
Patients with WBC greater than 25 x 109/L at presentation were pre-treated with hydroxyurea or leukapheresis.
Chemotherapy, induction
- Decitabine (Dacogen) 20 mg/m2 IV or SC once per day on days 1 to 5
- Venetoclax (Venclexta) 400, 800, or 1200 mg PO once per day
Variant #2, 10 days of decitabine
Study | Evidence |
---|---|
Maiti et al. 2018 (DEC10-VEN) | Phase II |
Therapy with hydroxyurea or one dose of cytarabine up to 2g/m2 was allowed during cycle 1.
Chemotherapy, induction
- Decitabine (Dacogen) 20 mg/m2 IV or SC once per day on days 1 to 10
- Venetoclax (Venclexta) 400, 800, or 1200 mg PO once per day
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 verified protocol 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 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. link to original abstract NCT03404193
Gemtuzumab ozogamicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Amadori et al. 2016 (EORTC/GIMEMA AML-19) | Phase III (E) | Best supportive care | Superior OS |
Chemotherapy
- Gemtuzumab ozogamicin (Mylotarg) 6 mg/m2 IV once on day 1, then 3 mg/m2 IV once on day 8
One 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. 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 verified protocol PubMed
Glasdegib & LoDAC
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Glasdegib & LoDAC: Glasdegib & Low Dose Ara-C (Cytarabine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cortes et al. 2018 (BRIGHT AML 1003) | Randomized Phase II (E) | LoDAC | Superior OS |
Chemotherapy
- Glasdegib (Daurismo) 100 mg PO once per day
- Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10
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
LoDAC
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LoDAC: Low Dose Ara-C (Cytarabine)
LDAC: Low-dose Ara-C (Cytarabine)
Variant #1, 20 mg twice per day, indefinite duration
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kantarjian et al. 2013 (SPARK-AML1) | Randomized Phase II (C) | Barasertib & LoDAC | Seems to have inferior OCRR |
Döhner et al. 2014 (BI 1230.4) | Randomized Phase II (C) | LoDAC & Volasertib | Seems to have inferior OS |
Cortes et al. 2018 (BRIGHT AML 1003) | Randomized Phase II (C) | Glasdegib & LoDAC | Inferior OS |
Chemotherapy
- Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10
28-day cycles
Variant #2, 20 mg/m2 twice per day, limited duration
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sekeres et al. 2012 (SG033-0003) | Randomized Phase II (C) | LDAC & Lintuzumab | Seems not superior |
Burnett et al. 2012 (UK NCRI AML16) | Phase III (C) | Clofarabine | Seems not superior (*) |
Dennis et al. 2015 | Randomized (C) | 1. LDAC & Vosaroxin | Seems not superior |
2. Vosaroxin | Seems not superior | ||
Burnett et al. 2015 | Randomized (C) | Sapacitabine | Might have inferior CR rate |
Dombret et al. 2015 (AZA-AML-001) | Phase III (C) | Azacitidine | Might have inferior OS |
Note: reported 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
Variant #3, 20 mg/m2 once per day, indefinite duration
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kantarjian et al. 2012 (DACO-016) | Phase III (C) | Decitabine | Might have inferior OS |
Chemotherapy
- Cytarabine (Ara-C) 20 mg/m2 SC once per day on days 1 to 10
28-day cycles until progression or intolerance
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 verified protocol link to PMC article 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. 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
- 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 verified protocol 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. link to original article contains verified protocol 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 protocol PubMed
- 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
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol PubMed
- 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 verified protocol link to PMC article 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. 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
LoDAC & Venetoclax
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LoDAC & Venetoclax: Low Dose Ara-C (Cytarabine) & Venetoclax
Regimen
Study | Evidence |
---|---|
Wei et. al. 2019 (M14-387) | Phase II |
Chemotherapy
- Cytarabine (Ara-C) 20 mg/m2 SC once per day on days 1 to 10
- Venetoclax (Venclexta) 600 mg PO once per day (dose reduction indicated when used when with CYP3A inhibitors)
28-day cycles
References
1. Wei AH, Strickland Jr SA, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. Journal of Clinical Oncology. 2019 Mar 20:JCO-18. link to abstract contains protocol
- NCT02287233 contains protocol
Temozolomide monotherapy
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Regimen
Study | Evidence |
---|---|
Brandwein et al. 2014 | Phase II |
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 protocol PubMed
Consolidation after upfront therapy
5+2d
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Regimen
Study | Evidence |
---|---|
Lancet et al. 2018 (CLTR0310-301) | Non-randomized portion of RCT |
Preceding treatment
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 protocol PubMed
HiDAC
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HiDAC: High Dose Ara-C (Cytarabine)
HDAC: High Dose Ara-C (Cytarabine)
HDAraC: High Dose AraC (Cytarabine)
Variant #1, 2000 mg/m2 every 12 hours x 6
Study | Evidence |
---|---|
Holowiecki et al. 2012 (PALG AML1/2004) | Non-randomized portion of RCT |
Details in the text are scant.
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1, 3, 5 (6 total doses)
Variant #2, 2 cycles of 2000 mg/m2 every 12 hours x 10
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fukushima et al. 2012 | Randomized, <20 pts in this arm (C) | mIDAC | Seems not superior |
Preceding treatment
- BHAC-MMV
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses)
2 cycles
Subsequent treatment
- A-VVV
Variant #3, 1 cycle of 3000 mg/m2 every 12 hours x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cassileth et al. 1998 | Phase III (C) | BuCy, then auto HSCT | Seems to have superior OS |
Preceding treatment
- 5+2i
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1 to 6 (12 total doses)
One course
Variant #4, 3 cycles of 3000 mg/m2 every 12 hours x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Moore et al. 2004 (CALGB 9222) | Phase III (C) | HiDAC, then CYVE, then AZQ & Mitoxantrone | Seems not superior |
Petersdorf et al. 2013 (SWOG S0106) | Non-randomized portion of RCT | ||
Schaich et al. 2013 (AML2003) | Phase III (C) | MAC/MAMAC/MAC | Seems not superior |
Stone et al. 2015 (ACCEDE) | Non-randomized portion of RCT | ||
Röllig et al. 2015 (SORAML) | Randomized Phase II (C) | HiDAC & Sorafenib | Seems to have inferior EFS |
Stone et al. 2015 (COSAH C-022) | Non-randomized portion of 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 (6 total doses)
3 cycles of varying durations
Subsequent treatment
- SWOG S0106: GO maintenance versus no further treatment
Variant #5, 3 cycles of 2000 mg/m2 every 12 hours x 10
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ohtake et al. 2010 (JALSG AML201) | Phase III (E) | Multiagent chemotherapy | Seems not superior |
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.
Preceding treatment
- 7+5d or 7+3i
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on days 1 to 5 (10 total doses)
3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 109/L, and 100 × 109/L
Variant #6, 4 cycles of 3000 mg/m2 every 12 hours x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mayer et al. 1994 (CALGB 8525) | Phase III (E) | Low-dose continuous infusion cytarabine | Seems to have superior OS |
Thomas et al. 2011 (ALFA-9802) | Phase III (C) | Timed sequential chemotherapy (TSC) | Seems not superior |
Lee et al. 2017 (COSAH C-022) | Non-randomized portion of RCT |
Preceding treatment
- ALFA-9802: Timed sequential therapy +/- GM-CSF priming
- 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 (6 total doses)
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; Cancer and Leukemia Group B. 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 verified protocol 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 verified protocol 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 verified protocol 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
- 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 verified protocol 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 verified protocol 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. link to original article contains verified protocol 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
- 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 verified protocol 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 verified protocol 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 verified protocol 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 protocol PubMed
- 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 verified protocol PubMed
IDAC
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IDAC: Intermediate Dose Ara-C (Cytarabine)
mIDAC: modified Intermediate Dose Ara-C (Cytarabine)
Variant #1, 1000 mg/m2 x 3
Study | Evidence |
---|---|
Stone et al. 2015 (ACCEDE) | Non-randomized portion of RCT |
Preceding treatment
- Amonafide & Cytarabine versus 7+3d (standard-dose)
- 7+3d & Glasdegib
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 3 hours once per day on days 1, 3, 5 (3 total doses)
Variant #2, 1000 mg/m2 x 10
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fukushima et al. 2012 | Randomized, <20 pts in this arm (E) | HDAC | Seems not superior |
Preceding treatment
- BHAC-MMV
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 60 minutes every 12 hours on days 1 to 5 (10 total doses)
Two cycles
Subsequent treatment
- A-VVV
Variant #3, 1000 mg/m2 x 12
Study | Evidence |
---|---|
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV over 6 hours every 12 hours on days 1 to 6 (12 total doses)
One cycle
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; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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 verified protocol 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. link to original article contains verified protocol 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 verified protocol PubMed
HDAC & G-CSF
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HDAC & G-CSF: High Dose Ara-C (Cytarabine) & Granulocyte Colony Stimulating Factor
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thomas et al. 2017 (ALFA-0702) | Randomized Phase II (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 (6 total doses)
- 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 verified protocol in supplement PubMed
Azacitidine monotherapy
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Regimen
Study | Evidence |
---|---|
Nand et al. 2013 (SWOG S0703) | Phase II |
Preceding treatment
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC once on day 1
28-day cycle for 4 cycles
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 verified protocol link to PMC article PubMed
Azacitidine & Gemtuzumab ozogamicin
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Regimen
Study | Evidence |
---|---|
Nand et al. 2013 (SWOG S0703) | Phase II |
Preceding treatment
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 IV once on day 8
Supportive medications
- "Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)
- Growth factors per physician discretion
1 cycle
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 verified protocol link to PMC article PubMed
BuCy, then auto HSCT
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BuCy: Busulfan & Cyclophosphamide
Variant #1, 16/120
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | Phase III (E) | 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
Variant #2, 16/200
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ravindranath et al. 1996 | Phase III (E) | Intensive chemotherapy | Seems not superior |
Preceding treatment
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -9 to -6
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days -5 to -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. link to original article contains verified protocol 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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol PubMed
BuFlu, then allo HSCT
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BuFlu: Busulfan & Fludarabine
Regimen
Study | Evidence |
---|---|
Devine et al. 2015 (CALGB 100103) | Phase II, <20 pts in subgroup |
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
- 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 verified protocol link to PMC article PubMed
CIA
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CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)
Regimen
Study | Evidence |
---|---|
Nazha et al. 2013 | Phase II |
Preceding treatment
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
3-day course; repeated every 3 to 4 weeks depending on disease response and recovery from regimen toxicity for up to six cycles
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 verified protocol link to PMC article PubMed
CLARA
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CLARA: CLofarabine and ARA-C (Cytarabine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thomas et al. 2017 (ALFA-0702) | Randomized Phase II (E) | HDAC & 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
- 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 verified protocol in supplement PubMed
Clofarabine & LoDAC/Decitabine
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Clofarabine & LoDAC/Decitabine: Clofarabine & Low Dose Ara-C (Cytarabine) alternating with Decitabine
Regimen
Study | Evidence |
---|---|
Faderl et al. 2010 | Phase II |
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 verified protocol 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
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CPX-351: Liposomal Cytarabine and Daunorubicin
Regimen
Study | Evidence |
---|---|
Lancet et al. 2018 (CLTR0310-301) | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- CPX-351 (Vyxeos) 65 units/m2 IV over 90 minutes once per day on days 1 & 3
Up to two courses
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 protocol PubMed
Cytarabine & Daunorubicin
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Variant #1
Study | Evidence |
---|---|
Castaigne et al. 2012 (ALFA-0701) | Non-randomized portion of 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. Length of courses is not specified.
Preceding treatment
- 7+3d (intermediate-dose) or 7+3d & GO induction
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 to 4 (8 total doses)
- Daunorubicin (Cerubidine) as follows:
- Course 1: 60 mg/m2 IV once on day 1
- Course 2: 60 mg/m2 IV once per day on days 1 & 2
2 courses
Variant #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gardin et al. 2007 (ALFA 9803) | Phase III (E) | 4 + 7 with daunorubicin | 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 (10 total doses)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once on day 1
1-month cycle for up to 6 cycles
References
- 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 verified protocol 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. link to original article contains verified protocol 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. link to original article link to PMC article PubMed
Cytarabine, Daunorubicin, Gemtuzumab ozogamicin
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Regimen
Study | Evidence |
---|---|
Castaigne et al. 2012 (ALFA-0701) | Non-randomized portion of RCT |
Note: length of courses is not specified.
Preceding treatment
- 7+3d & GO induction
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 to 4 (8 total doses)
- Daunorubicin (Cerubidine) as follows:
- Course 1: 60 mg/m2 IV once on day 1
- Course 2: 60 mg/m2 IV once per day on days 1 & 2
- Gemtuzumab ozogamicin (Mylotarg) 3 mg/m2 (maximum dose of 5 mg) IV once on day 1
2 courses
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 verified protocol 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. link to original article link to PMC article PubMed
CYVE
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CYVE: CYtarabine & VEpesid (Etoposide)
Regimen
Study | Evidence |
---|---|
Lee et al. 2017 (COSAH C-022) | Non-randomized portion of RCT |
Note: this consolidation regimen was for patients with high-risk cytogenetics.
Preceding treatment
- 7+3d (high-dose) versus 7+3i
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 verified protocol PubMed
Cytarabine & Idarubicin
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gardin et al. 2007 (ALFA 9803) | Phase III (E) | 4 + 7 with idarubicin | 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 (10 total doses)
- Idarubicin (Idamycin) 9 mg/m2 IV once on day 1
1-month cycle for up to 6 cycles
References
- 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 verified protocol PubMed
Cytarabine, Idarubicin, Sorafenib
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Regimen
Study | Evidence |
---|---|
Ravandi et al. 2010AML | Phase I/II |
Regimen details are from the phase II part of the published phase I/II trial. This trial should not be confused for the one by the same name in Ph+ B-ALL.
Preceding treatment
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
- 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
References
- 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 verified protocol link to PMC article 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. link to original article link to PMC article PubMed
Cyclophosphamide & TBI, then allo HSCT
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Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Evidence | Comparator | Efficacy | Non-relapse mortality |
---|---|---|---|---|
Blume et al. 1980 | Non-randomized, <20 pts | |||
Brochstein et al. 1987 | Non-randomized | |||
Zittoun et al. 1995 | Phase III (E) | Intensive chemotherapy | Superior DFS | |
Bornhäuser et al. 2012 | Phase III (C) | Fludarabine & TBI, then allo HSCT | Seems not superior | Seems not superior |
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
- Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. 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; European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. 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 protocol PubMed
- 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 protocol 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. link to original article link to PMC article PubMed
Etoposide & Mitoxantrone
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | Phase III (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
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; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (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 verified protocol PubMed
Fludarabine & TBI, then allo HSCT
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Variant #1
Study | Evidence | Comparator | Efficacy | Non-relapse mortality |
---|---|---|---|---|
Bornhäuser et al. 2012 | Phase III (E) | Cyclophosphamide & TBI, then allo HSCT | Seems not superior | Seems not superior |
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
Variant #2, low-dose TBI
Study | Evidence |
---|---|
Gyukocza et al. 2010 | 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
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 verified protocol link to PMC article PubMed
- 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 protocol PubMed
Fludarabine, Busulfan, ATG, then allo HSCT
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Regimen
Study | Evidence |
---|---|
Devine et al. 2015 (CALGB 100103) | Phase II |
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 verified protocol link to PMC article PubMed
HAM
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HAM: High-dose Ara-C (Cytarabine), Mitoxantrone
Regimen
Study | Evidence |
---|---|
Wierzbowksa et al. 2007 | Phase II |
Holowiecki et al. 2012 (PALG AML1/2004) | Non-randomized portion of RCT |
Preceding treatment
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
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 verified protocol 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 verified protocol PubMed
IC & Norethandrolone/6-MP, MTX, Norethandrolone
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IC & Norethandrolone: Idarubicin, Cytarabine, Norethandrolone
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pigneux et al. 2016 (GOELAMS LAM-SA2002) | Phase III (E) | 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)
Hormonotherapy, reinduction
- Norethandrolone (Nilevar) as follows:
- 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) as follows:
- If less than 60 kg: 20 mg PO twice per week in weeks 1 & 2
- If greater than 60 kg: 25 mg PO twice per week in weeks 1 & 2
- Mercaptopurine (6-MP) as follows:
- 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
Hormonotherapy, maintenance
- Norethandrolone (Nilevar) as follows:
- 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 verified protocol PubMed
Low-dose TBI, then allo HSCT
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TBI: Total Body Irradiation
Regimen
Study | Evidence |
---|---|
Gyukocza et al. 2010 | 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
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 verified protocol 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
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Regimen
Study | Evidence |
---|---|
Grövdal et al. 2010 | Phase II |
Intended to be used for transformed MDS patients in remission after AML induction therapy.
Preceding treatment
- 7+2d
Chemotherapy
- Azacitidine (Vidaza) 60 mg/m2 SC once per day on days 1 to 5
28-day cycles
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 verified protocol PubMed
Decitabine monotherapy
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Regimen
Study | Evidence |
---|---|
Blum et al. 2010 | Phase II |
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
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
- 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 verified protocol link to PMC article PubMed
Gemtuzumab ozogamicin monotherapy
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Regimen
Study | Evidence |
---|---|
Amadori et al. 2016 (EORTC/GIMEMA AML-19) | Non-randomized portion of RCT |
Preceding treatment
- Gemtuzumab ozogamicin induction, with clinical benefit
Chemotherapy
- 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. 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 verified protocol PubMed
LoDAC
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LoDAC: Low Dose Ara-C (cytarabine)
LDAC: Low Dose Ara-C (cytarabine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robles et al. 2000 (ECOG E5483) | Phase III (E) | Observation | Might have superior DFS |
Preceding treatment
- HiDAC, then amsacrine induction
Chemotherapy
- Cytarabine (Ara-C) 10 mg/m2 SC twice per day on days 1 to 21
8-week cycles
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 protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sauter et al. 1984 | Phase III (C) | Maintenance chemotherapy | Seems not superior |
Robles et al. 2000 (ECOG E5483) | Phase III (C) | LoDAC | Might have inferior DFS |
Breems et al. 2005 (HOVON/SAKK AML4) | Phase III (C) | Auto HSCT | Seems not superior |
Brune et al. 2006 | Phase III (C) | HDC/IL-2 | Inferior DFS |
Baer et al. 2002 (CALGB 9720) | Phase III (C) | Low-dose IL-2 | Seems not superior (*) |
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01) | Phase III (C) | Gemtuzumab ozogamicin | Seems not superior (*) |
Petersdorf et al. 2013 (SWOG S0106) | Phase III (C) | Gemtuzumab ozogamicin | Seems not superior |
Kolitz et al. 2013 (CALGB 19808) | Phase III (C) | Low-dose IL-2 | Seems not superior |
No further antineoplastic treatment. Reported efficacy for CALGB 9720 is based on the 2008 update. Reported efficacy for HOVON 43 AML/SAKK 30/01 is based on the 2010 update.
Preceding treatment
- ECOG E5483: HiDAC, then amsacrine induction
- HOVON 43 AML/SAKK 30/01: IDAC consolidation x 1
- SWOG S0106: HiDAC consolidation x 3
References
- Sauter C, Berchtold W, Fopp M, Gratwohl A, Imbach P, Maurice P, Tschopp L, von Fliedner V, Cavalli F. Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival. Lancet. 1984 Feb 18;1(8373):379-82. link to original article 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. link to original article contains protocol PubMed
- HOVON/SAKK AML4: Breems DA, Boogaerts MA, Dekker AW, Van Putten WL, Sonneveld P, Huijgens PC, Van der Lelie J, Vellenga E, Gratwohl A, Verhoef GE, Verdonck LF, Löwenberg B. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005 Jan;128(1):59-65. link to original article PubMed
- Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, Hogge DE, Nilsson B, Or R, Romero AI, Rowe JM, Simonsson B, Spearing R, Stadtmauer EA, Szer J, Wallhult E, Hellstrand K. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial. Blood. 2006 Jul 1;108(1):88-96. Epub 2006 Mar 23. 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 protocol PubMed
- 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
- 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 (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. 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 verified protocol PubMed
- Update: Löwenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, Ferrant A, Sonneveld P, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Breems D, de Muijnck H, Schaafsma R, Verhoef G, Döhner H, Gratwohl A, Pabst T, Ossenkoppele GJ, Maertens J; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); German Austrian AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010 Apr 1;115(13):2586-91. Epub 2010 Jan 26. link to original 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 PubMed
- CALGB 19808: Kolitz JE, George SL, Benson DM Jr, Maharry K, Marcucci G, Vij R, Powell BL, Allen SL, Deangelo DJ, Shea TC, Stock W, Bakan CE, Hars V, Hoke E, Bloomfield CD, Caligiuri MA, Larson RA; Alliance for Clinical Trials in Oncology. Recombinant interleukin-2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: results from Cancer and Leukemia Group B 19808. Cancer. 2014 Apr 1;120(7):1010-7. Epub 2013 Dec 31. link to original article link to PMC article PubMed
Sorafenib monotherapy
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Regimen
Study | Evidence |
---|---|
Ravandi et al. 2010AML | Phase I/II |
Note: This trial should not be confused for the one by the same name in Ph+ B-ALL.
Preceding treatment
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO twice per day
Up to one year of sorafenib therapy, including consolidation course(s)
References
- 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 verified protocol link to PMC article 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. 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
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Regimen
Study | Evidence |
---|---|
Zeidner et al. 2015 (JHOC-J1101) | Non-randomized portion of RCT |
Preceding treatment
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 verified protocol link to PMC article PubMed
ADE (standard-dose Ara-C)
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ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Milligan et al. 2006 (MRC AML-HR) | Phase III (C) | FLA | Seems to have superior OS |
Chemotherapy, Course 1
- Cytarabine (Ara-C) 100 mg/m2 IV push every 12 hours on days 1 to 10 (20 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push 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
Chemotherapy, Course 2
- Cytarabine (Ara-C) 100 mg/m2 IV push every 12 hours on days 1 to 8 (16 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push 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
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
CLAG
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CLAG: CLadribine, Ara-C (Cytarabine), G-CSF
Regimen
Study | Evidence |
---|---|
Robak et al. 2000 | Phase II |
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
- 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 verified protocol 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
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CLAG-M: CLadribine, Ara-C (Cytarabine), G-CSF, Mitoxantrone
Regimen
Study | Evidence |
---|---|
Wierzbowksa et al. 2007 | Phase II |
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
- Filgrastim (Neupogen) based on WBC count:
- 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
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 to 3
One course
Subsequent treatment
- Patients with PR were recommended to undergo a second course of CLAG-M.
- Primary refractory patients achieving CR after 2nd CLAG-M: HAM consolidation
- Others could receive another course of CLAG-M or HAM consolidation per investigator discretion
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 verified protocol 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
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CLARA: CLofarabine and ARA-C (Cytarabine)
GCLAC: G-CSF, Clofarabine, Ara-C (Cytarabine)
Regimen
Study | Evidence |
---|---|
Becker et al. 2011 | Phase II |
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
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days
One course with one re-induction allowed for patients with greater than 5% blasts at day 21
Subsequent treatment
- Patients achieving CR could receive consolidation with clofarabine reduced to 20 mg/m2, and cytarabine reduced to 1000 mg/m2, up to 2 cycles
References
- 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 verified protocol link to PMC article PubMed
Clofarabine & Cytarabine
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Variant #1, 20/20
Study | Evidence |
---|---|
Buckley et al. 2015 | Phase I/II |
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) as follows (per physician choice):
- 20 mg/m2 SC twice per day on days 1 to 10
- 20 mg/m2 SC once per day on days 1 to 14
Cycle duration not explicitly defined; presumably 28 days
Variant #2, 30/1000
Study | Evidence |
---|---|
Middeke et al. 2015 (BRIDGE) | Phase II |
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
Variant #3, 40/1000
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Faderl et al. 2004 | Phase I/II | ||
Agura et al. 2011 | Phase II | ||
Faderl et al. 2012 (CLASSIC I) | Phase III (E) | IDAC | Superior EFS |
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 medications
- 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
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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol 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 protocol PubMed
Cytarabine & Mitoxantrone
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MIDAC: Mitoxantrone & Intermediate-Dose Ara-C (Cytarabine)
Variant #1, 6000/25
Study | Evidence |
---|---|
Sternberg et al. 2000 | Phase II |
Chemotherapy
- Cytarabine (Ara-C) 500 mg/m2 IV over 90 minutes every 12 hours on days 1 to 6 (12 total doses)
- Mitoxantrone (Novantrone) 5 mg/m2 IV bolus once per day on days 1 to 5
One course
Variant #2, 10,000/48
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Solary et al. 1996 | Phase III (C) | Cytarabine, Mitoxantrone, Quinine | Seems not superior |
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV once every 12 hours on days 1 to 5 (10 total doses)
- Mitoxantrone (Novantrone) 12 mg/m2 IV bolus once per day on days 2 to 5
One 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 protocol 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 verified protocol PubMed
Etoposide & Mitoxantrone
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Ho et al. 1988 | Phase II | 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
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FLAG: FLudarabine, Ara-C (Cytarabine), G-CSF
Variant #1, weight-based G-CSF
Study | Evidence |
---|---|
Montillo et al. 1998 | Phase II |
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
- 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
One course
Variant #2, BSA-based G-CSF
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Kaspers et al. 2013 (I-BFM-SG 2001/01) | Phase III (C) | FLAG-DNX | Seems to have inferior CR rate |
Note: this regimen was studied in patients up to 21 years of age.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days 1 to 5, given second
- Cytarabine (Ara-C) 2000 mg/m2 IV once per day on days 1 to 5, given third, 4 hours after the start of fludarabine
- Filgrastim (Neupogen) 200 mcg/m2 (route not specified) once per day on days 0 to 5, given first
Two cycles
Subsequent treatment
- CYVE or Cytarabine & Thioguanine consolidation, as a bridge to allogeneic HSCT
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 verified protocol PubMed
- I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol PubMed
FLAG-Ida
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FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Filgrastim), Idarubicin
Regimen
Study | Evidence |
---|---|
Parker et al. 1997 | Phase II, <20 patients |
Pastore et al. 2003 | Phase II |
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
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery
- Idarubicin (Idamycin) 10 mg/m2 IV once per day on days 1 to 3
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. 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 protocol PubMed
F-SHAI
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F-SHAI: Fludarabine, Sequential High-dose Ara-C (cytarabine), Idarubicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fiegl et al. 2013 | Phase III (E) | 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 medications
- G-CSF 5 mcg/kg SC once per day from day 14 until ANC greater than 1500/uL
- Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts
One 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 verified protocol PubMed
HiDAC
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HiDAC: High Dose Ara-C (Cytarabine)
Variant #1, CI
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Giles et al. 2009 (VION-CLI-037) | Phase III (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)
One course
Variant #2, intermittent
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Karanes et al. 1999 | Phase III (C) | HiDAC & Mitoxantrone | Seems not superior |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on days 1 to 6
One course
References
- 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 SD article contains protocol 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 verified protocol PubMed
MEC
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MEC: Mitoxantrone, Etoposide, Cytarabine
Variant #1, 6/80/1000
Study | Evidence |
---|---|
Amadori et al. 1991 | Phase II |
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
One course
Variant #2, 8/80/1000
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Feldman et al. 2005 | Phase III (C) | MEC & Lintuzumab | Seems not superior |
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
One course
Variant #3, 8/100/1000
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Greenberg et al. 2004 (ECOG E2995) | Phase III (C) | MEC & Valspodar | Seems not superior |
Cortes et al. 2014 (CLTR0308-205) | Randomized Phase II (C) | CPX-351 | Seems not superior |
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
One course
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 verified protocol 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 verified protocol 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
Consolidation after salvage therapy
BuCy, then allo HSCT
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BuCy: Busulfan & Cyclophosphamide
Variant #1, 12.8/120
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rambaldi et al. 2015 | Phase III (C) | BuFlu, then allo HSCT | Seems to have inferior 1-year non-relapse mortality |
Scott et al. 2017 (BMT CTN 0901) | Phase III (E) | 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
Variant #2, 16/200
Study | Evidence |
---|---|
Santos et al. 1983 | 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
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 protocol PubMed
- 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
- 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
BuFlu, then allo HSCT
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BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rambaldi et al. 2015 | Phase III (E) | 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
Variant #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Andersson et al. 2008 | 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
Variant #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2013 | Phase III (E) | 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
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 verified protocol Pubmed
- 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 verified protocol PubMed
- 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
Clofarabine & Melphalan, then allo HSCT
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Regimen
Study | Evidence |
---|---|
Middeke et al. 2015 (BRIDGE) | Phase II |
Limited details are available in the abstract. Treatment is meant to be given during aplasia.
Preceding treatment
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 protocol PubMed
Cytarabine & Thioguanine
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Regimen
Study | Evidence |
---|---|
Kaspers et al. 2013 (I-BFM-SG 2001/01) | Non-randomized portion of RCT |
Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 75 mg/m2 SC once per day on days 1 to 4, every other week
- Thioguanine (Tabloid) 100 mg/m2 PO once per day for up to 4 weeks maximum
Subsequent treatment
- Allogeneic HSCT
References
- I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol PubMed
CYVE
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CYVE: CYtarabine & VEpesid (Etoposide)
Regimen
Study | Evidence |
---|---|
Kaspers et al. 2013 (I-BFM-SG 2001/01) | Non-randomized portion of RCT |
Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 500 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m2)
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days 1 to 4
Subsequent treatment
References
- I-BFM-SG 2001/01: Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. link to original article contains verified protocol 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
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Regimen
Study | Evidence |
---|---|
Thepot et al. 2010 | Phase II |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 7
28-day cycle for at least 4 to 6 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 (GFM). 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
Ruxolitinib monotherapy
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Regimen
Study | Evidence |
---|---|
Eghtedar et al. 2012 | Phase II |
Chemotherapy
- Ruxolitinib (Jakafi) 25 mg PO twice per day
28-day cycles
Patients with progression were allowed to increase the dose to 50 mg PO twice per day
References
- 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 verified protocol 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. Review. 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)
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- 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
Investigational agents
These are drugs under study with at least some promising results for this disease.
Additional information
Antifungal prophylaxis
- Review: Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015 Dec 24;126(26):2790-7. Epub 2015 Oct 26. link to original article link to PMC article PubMed