Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|aml}}
 
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Acute_myeloid_leukemia_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Acute myeloid leukemia - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
 
−
<big>'''Note: regimens tested in specific populations have been moved to dedicated pages:'''
 
−
*'''[[Acute_myeloid_leukemia,_FLT3-positive|AML, FLT3-positive]]'''
 
−
*'''[[Acute_myeloid_leukemia,_IDH-mutated|AML, IDH-mutated]]'''
 
−
*'''[[Acute_myeloid_leukemia,_NPM1-mutated|AML, NPM1-mutated]]'''
 
−
*'''[[Acute_myeloid_leukemia,_pediatric|Pediatric AML]]'''
 
−
</big>
 
−
{| class="wikitable" style="float:right; margin-right: 5px;"
 
−
|-
 
−
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
−
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
−
|}
 
−
{{TOC limit|limit=3}}
 
−
=Guidelines=
 
−
==ASH==
 
−
*'''2020:''' Sekeres et al. [https://ashpublications.org/bloodadvances/article/4/15/3528/461693/American-Society-of-Hematology-2020-guidelines-for American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults]
 
−
==ELN==
 
−
*'''2022:''' Döhner et al. [https://doi.org/10.1182/blood.2022016867 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN]
 
−
===Older===
 
−
*'''2017:''' Döhner et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel]
 
−
*'''2010:''' Döhner et al. [https://doi.org/10.1182/blood-2009-07-235358 Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet]
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2020:''' Heuser et al. [https://doi.org/10.1016/j.annonc.2020.02.018 Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
===Older===
 
−
*'''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"==
 
−
*'''2020:''' DeWolf & Tallman [https://doi.org/10.1182/blood.2019001982 How I treat relapsed or refractory AML]
 
−
*'''2020:''' DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. [https://doi.org/10.1182/blood.2019001239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31765470 PubMed]
 
−
*'''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://pubmed.ncbi.nlm.nih.gov/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://pubmed.ncbi.nlm.nih.gov/25778528 PubMed]
 
−
*'''2014:''' Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. [http://www.bloodjournal.org/content/125/5/767.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515963 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia]
 
−
==Antifungal prophylaxis==
 
−
*'''2022:''' Stemler et al. [https://doi.org/10.1016/S2352-3026(22)00073-4 Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association]
 
−
===Older===
 
−
*'''2015:''' Halpern et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia]
 
−
=Upfront induction therapy, standard and older "fit" patients=
 
−
''These are aggressive remission induction regimens given with curative intent.''
 
−
==7+3d (standard-dose) {{#subobject:9f31ad|Regimen=1}}==
 
−
7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
 
−
<br>AD: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>D</u>'''aunorubicin
 
−
<br>DA: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 700/135 (CI Ara-C) {{#subobject:bb27bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/4586956 Yates et al. 1973]
 
−
|NR in abstract
 
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="3" |[http://www.bloodjournal.org/content/58/6/1203.long Rai et al. 1981 (CALGB 7421)]
 
−
| rowspan="3" |1974-1975
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#7.2B3d_.28standard-dose.29|7+3d]]; bolus Ara-C)
 
−
| style="background-color:#91cf60" |Seems to have superior CR rate
 
−
|-
 
−
|2. [[#5.2B2d_88|5+2d]]
 
−
| style="background-color:#1a9850" |Superior CR rate
 
−
|-
 
−
|3. [[#5.2B2d_88|5+2d]]; bolus Ara-C
 
−
| style="background-color:#1a9850" |Superior CR rate
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1002/1097-0142(19820415)49:8%3C1530::aid-cncr2820490804%3E3.0.co;2-1 Omura et al. 1982]
 
−
| rowspan="2" |1974-1975
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#AVML_88|AVML]]
 
−
| style="background-color:#d3d3d3" |Not directly compared
 
−
|-
 
−
|2. [[Acute_myeloid_leukemia_-_historical#DAT|TAD]]
 
−
| style="background-color:#1a9850" |Superior time to CR
 
−
|-
 
−
| rowspan="2" |[http://www.bloodjournal.org/content/60/2/454.long Yates et al. 1982 (CALGB 7721)]
 
−
| rowspan="2" |1977-1979
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Acute_myeloid_leukemia_-_historical#7.2B3d_.28low-dose.29|7+3d (low-dose)]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|2. [[#7.2B3a_99|7+3a]]; 30 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/63/5/1039.long Vogler et al. 1984]
 
−
|1977-1981
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="2" |[http://www.bloodjournal.org/content/69/5/1441.long Preisler et al. 1987 (CALGB 7921)]
 
−
| rowspan="2" |1979-1982
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#10.2B3d_99|10+3d]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|2. [[Acute_myeloid_leukemia_-_historical#DAT|TAD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/10.1016/0145-2126(90)90179-d Stein et al. 1990]
 
−
|1982-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Amsacrine_.26_Cytarabine_99|MA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/2179638 Arlin et al. 1990]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3m|7+3m]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/78/10/2520.long Dillman et al. 1991 (CALGB 8321)]
 
−
|1982-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; higher-dose Ara-C
 
−
| style="background-color:#ffffbf" |Did not meet primary efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/79/2/313 Wiernik et al. 1992]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3i|7+3i]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1992.10.7.1103 Vogler et al. 1992]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3i|7+3i]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR rate
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004 (ECOG E3993)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#7.2B3d_.26_GM-CSF_99|7+3d & GM-CSF]]<br> 2. [[#7.2B3i|7+3i]]<br> 3. [[#7.2B3i_.26_GM-CSF_99|7+3i & GM-CSF]]<br> 4. [[#7.2B3m|7+3m]]<br> 5. [[#7.2B3m_.26_GM-CSF_99|7+3m & GM-CSF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/full/10.1111/j.1365-2141.2008.07400.x Latagliata et al. 2008 (GIMEMA GSI 103 AMLE)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3dnx_99|7+3 (Daunoxome)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2993615/ Cripe et al. 2010 (ECOG E3999)]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_Zosuquidar_77|7+3d & Zosuquidar]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ Fernandez et al. 2009 (ECOG E1900)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Azacitidine_monotherapy|Azacitidine]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
''Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3i|7+3i]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 700/150 (CI Ara-C) {{#subobject:9934a6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/75/1/27.long Bishop et al. 1990]
 
−
|1984-1987
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADE_.28standard-dose_Ara-C.29|ADE]]; standard-dose
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1120/120 (intermittent Ara-C) {{#subobject:1f1bb5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/8916311 Masaoka et al. 1996]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#7.2B3i|7+3i]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 1400/135 (CI Ara-C) {{#subobject:635ecb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/78/10/2520.long Dillman et al. 1991 (CALGB 8321)]
 
−
|1982-1986
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; lower-dose Ara-C
 
−
| style="background-color:#ffffbf" |Did not meet primary efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/88/8/2841.long Weick et al. 1996]
 
−
|1986-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HiDAC.2B3d_88|HiDAC+3d]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1996.14.7.2150 Zittoun et al. 1996 (AML 8B)]
 
−
|1986-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_GM-CSF_99|7+3d & GM-CSF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary efficacy endpoint
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ Moore et al. 2004 (CALGB 9222)]
 
−
|1992-1995
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/100/12/3869.long Anderson et al. 2002 (SWOG S9333)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#ME|ME]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
 
−
|2000-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
| style="background-color:#d73027" |Inferior CR rate
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/14/3832.long Lee et al. 2011 (ADcomparison)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2014.57.0952 Stone et al. 2015 (ACCEDE)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CALGB 9222: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus multi-agent [[Regimen_classes#Chemotherapy|chemotherapy]] consolidation
 
−
*HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation
 
−
*ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] if younger than 60 or [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] if greater than or equal to 60.
 
−
</div></div>
 
−
===References===
 
−
#Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. [https://pubmed.ncbi.nlm.nih.gov/4586956 PubMed]
 
−
#'''CALGB 7421:''' Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. [http://www.bloodjournal.org/content/58/6/1203.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6946847 PubMed]
 
−
#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://doi.org/10.1002/1097-0142(19820415)49:8%3C1530::aid-cncr2820490804%3E3.0.co;2-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7039813 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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6953986 PubMed]
 
−
#Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L; SECSG. A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial. Blood. 1984 May;63(5):1039-45. [http://www.bloodjournal.org/content/63/5/1039.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/6201211 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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3552076 PubMed]
 
−
#Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A; Southeastern Cancer Study Group. Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial. Leuk Res. 1990;14(10):895-903. [https://doi.org/10.1016/0145-2126(90)90179-d link to original article] [https://pubmed.ncbi.nlm.nih.gov/2259226 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2403818 PubMed]
 
−
#Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. [https://pubmed.ncbi.nlm.nih.gov/2179638 PubMed]
 
−
#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1824249 PubMed]
 
−
#Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1730080 PubMed]
 
−
#Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. [https://doi.org/10.1200/JCO.1992.10.7.1103 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1607916 PubMed]
 
−
#'''AML 8B:''' Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, Hayat M, Peetermans M, Cadiou M, Solbu G, Petti MC, Willemze R. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996 Jul;14(7):2150-9. [https://doi.org/10.1200/jco.1996.14.7.2150 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8683249/ PubMed] NCT01324063
 
−
##'''Update:''' Hengeveld M, Suciu S, Karrasch M, Specchia G, Marie JP, Muus P, Petti MC, Rotoli B, Amadori S, Fioritoni G, Leoni P, Morra E, Thaler J, Resegotti L, Fazi P, Vignetti M, Mandelli F, Zittoun R, de Witte T; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organisation for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. Ann Hematol. 2012 Jun;91(6):825-35. Epub 2012 Mar 31. [https://doi.org/10.1007/s00277-012-1436-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345117/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22460947 PubMed]
 
−
#Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8916311 PubMed]
 
−
#Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M; [[Study_Groups#SWOG|SWOG]]. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51. [http://www.bloodjournal.org/content/88/8/2841.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8874180 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12393614 PubMed]
 
−
#'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052
 
−
#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15572587 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://doi.org/full/10.1111/j.1365-2141.2008.07400.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18950458 PubMed]
 
−
#'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology; AMLSG; Swiss Group for Clinical Cancer Research. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377
 
−
#'''ECOG E1900:''' Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. [https://doi.org/10.1056/NEJMoa0904544 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19776406 PubMed] NCT00049517
 
−
##'''Update:''' Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. [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://pubmed.ncbi.nlm.nih.gov/26755712 PubMed]
 
−
#'''ECOG E3999:''' Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Luger S, Tallman MS. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood. 2010 Nov 18;116(20):4077-85. Epub 2010 Aug 17. [https://doi.org/10.1182/blood-2010-04-277269 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2993615/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20716770/ PubMed] NCT00046930
 
−
#'''ADcomparison:''' Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. Epub 2011 Aug 9. [http://www.bloodjournal.org/content/118/14/3832.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21828126 PubMed] NCT00474006
 
−
#'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637
 
−
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 
−
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 
−
==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}==
 
−
7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.42.2907 Büchner et al. 2012 (OSHO 061)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|See paper for details
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.46.4743 Schaich et al. 2013 (AML2003)]
 
−
|2003-2009
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288671/ Walker et al. 2021 (CALGB 10201)]
 
−
|2004-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_Oblimersen_77|7+3d & Oblimersen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ Petersdorf et al. 2013 (SWOG S0106)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_GO|7+3d & GO]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.46.4990 Serve et al. 2013 (AML2006)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00362-9 Röllig et al. 2015 (SORAML)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|[https://www.nature.com/articles/leu2015306 Müller-Tidow et al. 2015 (AML-AZA)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_Azacitidine_99|7+3d & Azacitidine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Azacitidine_monotherapy|Azacitidine]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ Lancet et al. 2018 (CLTR0310-301)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CPX-351_monotherapy|CPX-351]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
**Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*AML2003: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus [[#MAC.2FMAMAC.2FMAC_99|MAC/MAMAC/MAC]] consolidation
 
−
*CALGB 10201: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2
 
−
*SWOG S0106: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3
 
−
*CLTR0310-301: [[#5.2B2d|5+2d]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:cf53dd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.leu.2403336 Holowiecki et al. 2004 (PALG AML1/1999)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DAC|DAC]]
 
−
| style="background-color:#d73027" |Inferior CR rate after first induction
 
−
|-
 
−
|[https://www.nature.com/articles/leu2010111 Chevallier et al. 2010 (LAM-2001)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Acute_myeloid_leukemia_-_historical#7.2B5i|7+5i]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of LFS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2011.37.1286 Holowiecki et al. 2012 (PALG AML1/2004)]
 
−
| rowspan="2" |2004-2008
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#DAC|DAC]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|2. [[#DAF_88|DAF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)60485-1 Castaigne et al. 2012 (ALFA-0701)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.26_GO|7+3d & GO]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*"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
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====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 in remission in both PALG studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 
−
*ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed]
 
−
#'''LAM-2001:''' Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. [https://www.nature.com/articles/leu2010111 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20508614 PubMed]
 
−
##'''Update:''' Récher C, Béné MC, Lioure B, Pigneux A, Vey N, Delaunay J, Luquet I, Hunault M, Guyotat D, Bouscary D, Fegueux N, Jourdan E, Lissandre S, Escoffre-Barbe M, Bonmati C, Randriamalala E, Guièze R, Ojeda-Uribe M, Dreyfus F, Harousseau JL, Cahn JY, Ifrah N, Guardiola P; Groupe Ouest-Est d’ étude des Leucé mies Aiguës et autres. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia. Leukemia. 2014 Feb;28(2):440-3. Epub 2013 Oct 9. [https://www.nature.com/articles/leu2013290 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24166215 PubMed]
 
−
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 
−
#'''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://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 
−
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 
−
#'''OSHO 061:''' Büchner T, Schlenk RF, Schaich M, Döhner K, Krahl R, Krauter J, Heil G, Krug U, Sauerland MC, Heinecke A, Späth D, Kramer M, Scholl S, Berdel WE, Hiddemann W, Hoelzer D, Hehlmann R, Hasford J, Hoffmann VS, Döhner H, Ehninger G, Ganser A, Niederwieser DW, Pfirrmann M. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol. 2012 Oct 10;30(29):3604-10. Epub 2012 Sep 10. [https://doi.org/10.1200/jco.2012.42.2907 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22965967/ PubMed] NCT01414231
 
−
#'''AML2003:''' Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. [https://doi.org/10.1200/JCO.2012.46.4743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23630210 PubMed] NCT00180102
 
−
#'''AML2006:''' Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, Schaich M, Ottmann O, Duyster J, Wandt H, Fischer T, Giagounidis A, Neubauer A, Reichle A, Aulitzky W, Noppeney R, Blau I, Kunzmann V, Stuhlmann R, Krämer A, Kreuzer KA, Brandts C, Steffen B, Thiede C, Müller-Tidow C, Ehninger G, Berdel WE. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013 Sep 1;31(25):3110-8. Epub 2013 Jul 29. [https://doi.org/10.1200/JCO.2012.46.4990 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23897964 PubMed] NCT00373373
 
−
#'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709
 
−
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 
−
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 
−
#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26522083 PubMed] NCT00915252
 
−
#'''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://doi.org/10.1016/S1470-2045(15)00362-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26549589 PubMed] NCT00893373
 
−
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 
−
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 
−
##'''Update:''' Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. [https://doi.org/10.1016/s2352-3026(21)00134-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34171279/ PubMed]
 
−
#'''CALGB 10201:''' Walker AR, Marcucci G, Yin J, Blum W, Stock W, Kohlschmidt J, Mrózek K, Carroll AJ, Eisfeld AK, Wang ES, Jacobson S, Kolitz JE, Thakuri M, Sutamtewagul G, Vij R, Stuart RK, Byrd JC, Bloomfield CD, Stone RM, Larson RA. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance). Blood Adv. 2021 Jul 13;5(13):2775-2787. [https://doi.org/10.1182/bloodadvances.2021004233 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288671/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34251414 PubMed] NCT00085124.
 
−
#'''AMLSG31-19:''' NCT04628026
 
−
#'''ECOG E2906:''' NCT02085408
 
−
#'''ENHANCE-2:''' NCT04778397
 
−
==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}==
 
−
7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 700/270 {{#subobject:70583e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ Fernandez et al. 2009 (ECOG E1900)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 23.7 vs 15.7 mo<br>(HR 0.74, 95% CI 0.60-0.90)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ Zeidner et al. 2015 (JHOC-J1101)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#FLAM_88|FLAM]]
 
−
| style="background-color:#d73027" |Inferior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*JHOC-J1101: Patients with residual leukemia at day 14 underwent [[#5.2B2d_2|5+2d]] salvage
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1400/240 {{#subobject:a33bec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/8/2467.long Castaigne et al. 2004 (ALFA 9000)]
 
−
|1990-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#7.2B3d_.28high-dose.29|7+3d]] x 2<br> 2. Timed sequential induction
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFI
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1400/270 {{#subobject:664ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
 
−
|2000-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
| style="background-color:#1a9850" |Superior CR rate
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/14/3832.long Lee et al. 2011 (ADcomparison)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS60: 46.8% vs 34.6%<br>(HR 0.74, 95% CI 0.58-0.97)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3i|7+3i]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation
 
−
*COSAH C-022, with CR, good- or intermediate-risk cytogenetics: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 
−
*COSAH C-022, with CR, high-risk cytogenetics: [[#Cytarabine_.26_Etoposide_88|Cytarabine & etoposide]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA 9000:''' Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. [http://www.bloodjournal.org/content/104/8/2467.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15142880 PubMed]
 
−
#'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377
 
−
#'''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://doi.org/10.1056/NEJMoa0904544 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19776406 PubMed] NCT00049517
 
−
##'''Update:''' Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. [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://pubmed.ncbi.nlm.nih.gov/26755712 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21828126 PubMed] NCT00474006
 
−
#'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972
 
−
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 
−
==7+3d & GO {{#subobject:869f84|Regimen=1}}==
 
−
7+3d & GO: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, split GO dosing {{#subobject:4c0a05|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)60485-1 Castaigne et al. 2012 (ALFA-0701)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS24: 53.2% vs 41.9%<br>(HR 0.69, 95% CI 0.49-0.98)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====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 less than 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, single-day GO {{#subobject:4ug8f5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ Petersdorf et al. 2013 (SWOG S0106)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
''Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV over 2 hours once on day 4
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 
−
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 
−
#'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709
 
−
==7+3i {{#subobject:717935|Regimen=1}}==
 
−
7+3i: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin
 
−
<br>AI: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>I</u>'''darubicin
 
−
<br>IA: '''<u>I</u>'''darubicin & '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 80/12, intermittent Ara-C {{#subobject:bdc11c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/8916311 Masaoka et al. 1996]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
| style="background-color:#91cf60" |Seems to have superior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 100/12, CI Ara-C {{#subobject:c6cda|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/0277-5379(91)90181-C Mandelli et al. 1991]
 
−
|1984-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1992.10.7.1103 Vogler et al. 1992]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]
 
−
| style="background-color:#91cf60" |Seems to have superior CR rate
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/8290968 Haas et al. 1993]
 
−
|1989-NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004 (ECOG E3993)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose<br> 2. [[#7.2B3d_.26_GM-CSF_99|7+3d + GM-CSF]]<br> 3. [[#7.2B3i_.26_GM-CSF_99|7+3i + GM-CSF]]<br> 4. [[#7.2B3m|7+3m]]<br> 5. [[#7.2B3m_.26_GM-CSF_99|7+3m + GM-CSF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/10.1007/s12185-009-0480-5 Ohtake et al. 2010 (JALSG AML95)]
 
−
|1995-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Individualized chemotherapy
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.21493 Miyawaki et al. 2005 (JALSG AML97)]
 
−
|1997-2001
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/117/8/2358 Ohtake et al. 2010 (JALSG AML201)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#7.2B5d|7+5d]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> 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.''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 100/13, CI Ara-C {{#subobject:7f2eec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/79/2/313 Wiernik et al. 1992]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Idarubicin (Idamycin)]] 13 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 200/12, CI Ara-C {{#subobject:f33de6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa025406 Löwenberg et al. 2003 (HOVON/SAKK AML 29)]
 
−
|1995-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3i_.26_G-CSF_88|7+3i & G-CSF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.23.2652 Pautas et al. 2010 (ALFA-9801)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose<br> 2. [[Stub#7.2B4i|7+4i]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1010222 Löwenberg et al. 2011 (HOVON/SAKK AML 42)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HiDAC.2B3i_99|HiDAC+3i]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/129/12/1636.long Löwenberg et al. 2017 (HOVON-102)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#7.2B3i_.26_Clofarabine|7+3i & Clofarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior CR rate
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7903238/ Löwenberg et al. 2021 (HOVON/SAKK-132)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#7.2B3i_.26_Lenalidomide|7+3i & Lenalidomide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
 
−
**Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*HOVON/SAKK AML 29 & AML 42: [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]]
 
−
*ALFA-9801, patients achieiving CR: [[#Cytarabine_.26_Idarubicin_2|cytarabine & idarubicin]] consolidation
 
−
*COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 
−
*COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE]] consolidation
 
−
*HOVON/SAKK-132: [[#Daunorubicin_.26_IDAC|Daunorubicin & IDAC]] (remission induction cycle II)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, with range {{#subobject:eb0168|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Azacitidine_monotherapy|Azacitidine]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Idarubicin (Idamycin)]] 9 to 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div>
 
−
===References===
 
−
#Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. [https://www.ejcancer.com/article/0277-5379(91)90181-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/1829918 PubMed]
 
−
#Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1730080 PubMed]
 
−
#Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. [https://doi.org/10.1200/JCO.1992.10.7.1103 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1607916 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://pubmed.ncbi.nlm.nih.gov/8290968 PubMed]
 
−
#Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8916311 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://doi.org/10.1056/NEJMoa025406 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12930926 PubMed]
 
−
#'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052
 
−
#'''JALSG AML97:''' Miyawaki S, Sakamaki H, Ohtake S, Emi N, Yagasaki F, Mitani K, Matsuda S, Kishimoto Y, Miyazaki Y, Asou N, Matsushima T, Takahashi M, Ogawa Y, Honda S, Ohno R; Japan Adult Leukemia Study Group. A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 study. Cancer. 2005 Dec 15;104(12):2726-34. [https://doi.org/full/10.1002/cncr.21493 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16284985 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. [https://doi.org/10.1200/JCO.2009.23.2652 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20048183 PubMed] NCT00931138
 
−
#'''JALSG AML95:''' Ohtake S, Miyawaki S, Kiyoi H, Miyazaki Y, Okumura H, Matsuda S, Nagai T, Kishimoto Y, Okada M, Takahashi M, Handa H, Takeuchi J, Kageyama S, Asou N, Yagasaki F, Maeda Y, Ohnishi K, Naoe T, Ohno R. Randomized trial of response-oriented individualized versus fixed-schedule induction chemotherapy with idarubicin and cytarabine in adult acute myeloid leukemia: the JALSG AML95 study. Int J Hematol. 2010 Mar;91(2):276-83. [https://doi.org/10.1007/s12185-009-0480-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20054669 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://pubmed.ncbi.nlm.nih.gov/20693429 PubMed] C000000157
 
−
#'''HOVON/SAKK AML 42:''' Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ; HOVON; SAKK. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. [https://doi.org/10.1056/NEJMoa1010222 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21410371 PubMed] NTR230
 
−
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 
−
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 
−
#'''HOVON-102:''' Löwenberg B, Pabst T, Maertens J, van Norden Y, Biemond BJ, Schouten HC, Spertini O, Vellenga E, Graux C, Havelange V, de Greef GE, de Weerdt O, Legdeur MJ, Kuball J, Kooy MV, Gjertsen BT, Jongen-Lavrencic M, van de Loosdrecht AA, van Lammeren-Venema D, Hodossy B, Breems DA, Chalandon Y, Passweg J, Valk PJ, Manz MG, Ossenkoppele GJ; HOVON; SAKK. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML. Blood. 2017 Mar 23;129(12):1636-1645. Epub 2017 Jan 3. [http://www.bloodjournal.org/content/129/12/1636.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28049642 PubMed] NTR2187
 
−
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 
−
# '''HOVON/SAKK-132:''' Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. [https://doi.org/10.1182/bloodadvances.2020003855 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7903238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33616652/ PubMed]
 
−
# '''SWOG S1203:''' NCT01802333
 
−
==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:567ab9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010 (BAY43-9006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**60 and younger: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m<sup>2</sup>)
 
−
**Older than 60: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m<sup>2</sup>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib]] consolidation
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 
−
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 
−
==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0e6b97|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ Cortes et al. 2018 (B1371003)]
 
−
|2012-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: glasdegib is continued beyond induction; see paper for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Targeted therapy====
 
−
*[[Glasdegib (Daurismo)]] 100 mg PO once per day, started on day -3
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''B1371003:''' Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. [https://doi.org/10.1002/ajh.25238 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30074259 PubMed] NCT01546038
 
−
==7+3m {{#subobject:240c72|Regimen=1}}==
 
−
7+3m: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>m</u>'''itoxantrone
 
−
<br>MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7d87af|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/2179638 Arlin et al. 1990]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#7.2B3d_.28standard-dose.29|7+3d]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004 (ECOG E3993)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose<br> 2. [[#7.2B3d_.26_GM-CSF_99|7+3d + GM-CSF]]<br> 3. [[#7.2B3i|7+3i]]<br> 4. [[#7.2B3i_.26_GM-CSF_99|7+3i + GM-CSF]]<br> 5. [[#7.2B3m_.26_GM-CSF_99|7+3m + GM-CSF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3m|7+3m]]
 
−
</div></div>
 
−
===References===
 
−
#Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. [https://pubmed.ncbi.nlm.nih.gov/2179638 PubMed]
 
−
#'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052
 
−
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
 
−
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
−
<br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
−
<br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 7-3-7, 700/150/525 {{#subobject:386fd2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/87/5/1710.long Bishop et al. 1996]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADE_.28high-dose_Ara-C.29|ADE (high-dose Ara-C)]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
 
−
'''7-day course; can be repeated up to 3 times if CR not achieved'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*5-2-5 consolidation x 2
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 7-3-3, 700/180/300 {{#subobject:31dcd2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/100/4/1224.long Baer et al. 2002 (CALGB 9720)]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADEP_99|ADEP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 7-3-3, 700/270/300 {{#subobject:3gh1d2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2938834/ Kolitz et al. 2010 (CALGB 19808)]
 
−
|2001-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADEP_99|ADEP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C {{#subobject:7ce6f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.51.8571 Willemze et al. 2013 (EORTC-GIMEMA AML-12)]
 
−
|1999-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADE_.28high-dose_Ara-C.29|ADE (high-dose Ara-C)]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''10-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C {{#subobject:7ce6f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773224/ Mandelli et al. 2009 (EORTC-GIMEMA AML-10)]
 
−
|1993-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AIE_99|AIE]]<br> 2. [[Stub#AME|AME]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''10-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/7/2311.long Hann et al. 1997 (UK MRC AML10)]
 
−
|1988-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Acute_myeloid_leukemia_-_historical#DAT|DAT 3+8]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|}
 
−
''Note: these trials have complicated treatment schemas; see papers for details.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*UK MRC AML10: MACE consolidation
 
−
*UK MRC AML15: Consolidation (see paper for details)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/7/2311.long Hann et al. 1997 (UK MRC AML10)]
 
−
|1988-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Acute_myeloid_leukemia_-_historical#DAT|DAT 3+10]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[http://www.bloodjournal.org/content/93/12/4131.long Burnett et al. 1999 (UK MRC AML12)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML12|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML12|See link]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|}
 
−
''Note: these trials have complicated treatment schemas; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction
 
−
</div></div>
 
−
===References===
 
−
#Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed]
 
−
#'''UK MRC AML10:''' Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed]
 
−
##'''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://doi.org/10.1016/S0140-6736(97)09214-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9504514 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://pubmed.ncbi.nlm.nih.gov/10361110 PubMed] NCT00002658
 
−
##'''Update:''' Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.22.9088 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20038732 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12149202 PubMed] NCT00003190
 
−
##'''Update:''' Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K, Kolitz JE, Powell BL, Moore JO, Stone RM, Anastasi J, Bloomfield CD, Larson RA. Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720. J Clin Oncol. 2008 Oct 20;26(30):4934-9. Epub 2008 Jun 30. [https://doi.org/10.1200/JCO.2008.17.0472 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652081/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18591543 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; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol. 2009 Nov 10;27(32):5397-403. Epub 2009 Oct 13. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1438. [https://doi.org/10.1200/JCO.2008.20.6490 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773224/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19826132 PubMed]
 
−
##'''Update:''' Baron F, Efficace F, Cannella L, Muus P, Trisolini S, Halkes CJM, Fazi P, Vignetti M, Marie JP, Chiusolo P, van der Velden W, La Sala E, Vitolo U, Thomas X, Lefrère F, Di Raimondo F, Bourhis JH, Specchia G, Guimarães JE, Allione B, Vrhovac R, Ferrara F, Stevens-Kroef M, Meert L, de Witte T, Willemze R, Amadori S, Suciu S. Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study. Am J Hematol. 2020 Jul;95(7):749-758. Epub 2020 Apr 17. [https://doi.org/10.1002/ajh.25795 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32233095 PubMed]
 
−
#'''CALGB 19808:''' Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. Epub 2010 Jun 3. [https://doi.org/10.1182/blood-2009-07-229492 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2938834/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20522709/ PubMed] NCT00006363
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
<!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
 
−
#'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128
 
−
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
 
−
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
−
<br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, HIDAC-3-5 {{#subobject:b1a101|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.51.8571 Willemze et al. 2013 (EORTC-GIMEMA AML-12)]
 
−
|1999-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ADE_.28standard-dose_Ara-C.29|ADE (standard-dose Ara-C)]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS72: 42.5% vs 38.7%<br>(HR 0.89, 95% CI 0.79-1.00)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''7-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, HIDAC-3-7 {{#subobject:386df8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/87/5/1710.long Bishop et al. 1996]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ADE_.28standard-dose_Ara-C.29|ADE (standard-dose Ara-C)]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
 
−
'''7-day course; can be repeated up to 3 times if CR not achieved'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*5-2-5 consolidation x 2
 
−
</div></div>
 
−
===References===
 
−
#Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed]
 
−
<!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
 
−
#'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128
 
−
==AIE {{#subobject:948b49|Regimen=1}}==
 
−
AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide
 
−
<br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c7b35a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/2/481.long Bradstock et al. 2004 (ALLG M7)]
 
−
|1995-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948102/ de Witte et al. 2010 (CRIANT)]
 
−
|1996-2003
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.nature.com/articles/2403528 Schlenk et al. 2004]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#A-ICE|A-ICE]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/full/10.1111/j.1365-2141.2005.05745.x Russo et al. 2005]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#FLAI|FLAI]]
 
−
| style="background-color:#d73027" |Inferior CR rate
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212/ Bassan et al. 2019 (NILG AML 02/06)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Sequential high-dose therapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ALLG M7: ICE versus IcE consolidation
 
−
*NILG AML 02/06, early CR: IC consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''ALLG M7:''' Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. [http://www.bloodjournal.org/content/105/2/481.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15213095 PubMed]
 
−
#Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. [https://www.nature.com/articles/2403528 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15385923 PubMed]
 
−
#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://doi.org/full/10.1111/j.1365-2141.2005.05745.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://pubmed.ncbi.nlm.nih.gov/20494931 PubMed] NCT00002926
 
−
#'''NILG AML 02/06:''' Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. [http://www.bloodadvances.org/content/3/7/1103.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30948365 PubMed] NCT00495287
 
−
==CIA {{#subobject:de6dec|Regimen=1}}==
 
−
CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ Jabbour et al. 2017 (MDACC 2010-0788)]
 
−
|2011-2016
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[Stub#FLAI|FIA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
'''5-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients not achieving CR or CRp: Optional second [[#CIA|CIA]] induction
 
−
*Patients achieving CR or CRp: [[#CIA_2|CIA]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 20/10/1000 {{#subobject:4a7d81|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ Nazha et al. 2013]
 
−
|2010-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Levofloxacin (Levaquin)]]
 
−
*[[Itraconazole (Sporanox)]]
 
−
*[[Valacyclovir (Valtrex)]]
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion
 
−
'''5-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR: a second course with the same drugs, doses, and schedule.
 
−
*Patients achieving CR or CRi: [[#CIA_2|CIA]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed]
 
−
#'''MDACC 2010-0788:''' Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. [https://doi.org/10.1002/cncr.30883 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28708931 PubMed] NCT01289457
 
−
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
 
−
DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.42.2964 Burnett et al. 2012 (UK NCRI AML16)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DA_3_.2B_10.2C_GO|DA 3 + 10, GO]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See papers for details (to be completed).
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 60 mg/m<sup>2</sup> dauno {{#subobject:211741|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DA_3_.2B_10|DA 3 + 10]]; high-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this regimen is very similar to [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CBF: [[#DA_3.2B8_.26_GO|DA 3+8 & GO]]
 
−
*Non-CBF, no FLT3 mutation, not poor risk: [[#DA_3.2B8|DA 3+8]] versus DA 3+8 & Everolimus
 
−
*Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus [[#FLAG-Ida_2|FLAG-Ida]]
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
#'''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. [https://doi.org/10.1200/jco.2012.42.2964 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22851554 PubMed] ISRCTN11036523
 
−
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 
−
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
 
−
##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed]
 
−
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
 
−
DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6a938e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.42.2964 Burnett et al. 2012 (UK NCRI AML16)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#DA_3_.2B_10|DA 3 + 10]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS36: 25% vs 20%<br>(HR 0.87, 95% CI 0.76-1.00)
 
−
|-
 
−
|}
 
−
''Both trials have complicated treatment schemas; see papers for details.''
 
−
====Chemotherapy====
 
−
*[[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
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details (to be completed).
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
#'''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. [https://doi.org/10.1200/jco.2012.42.2964 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22851554 PubMed] ISRCTN11036523
 
−
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 
−
==DAC {{#subobject:9b1553|Regimen=1}}==
 
−
DAC: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''ladribine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f00b8a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.leu.2403336 Holowiecki et al. 2004 (PALG AML1/1999)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3d_.28intermediate-dose.29|DA]]
 
−
| style="background-color:#1a9850" |Superior CR rate after first induction
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2011.37.1286 Holowiecki et al. 2012 (PALG AML1/2004)]
 
−
| rowspan="2" |2004-2008
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#7.2B3d_.28intermediate-dose.29|DA]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 24 vs 14 mo<br>(HR 0.69, 97.5% CI 0.5-0.96)
 
−
|-
 
−
|2. [[#DAF_88|DAF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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>)
 
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*"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
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====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|CLAG]] salvage
 
−
*Patients in remission in both studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed]
 
−
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 
−
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
 
−
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:44e85e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ADE_.28standard-dose_Ara-C.29|ADE 10+3+5]]<br> 2. [[#DA_3_.2B_10|DA 3+10]]<br> 3. [[#DA_3_.2B_10.2C_GO|DA 3+10 & GO]]<br> 4. [[#FLAG-Ida_.26_GO_99|FLAG-Ida & GO]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
 
−
====Growth factor therapy====
 
−
*[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
==HAA {{#subobject:0788e0|Regimen=1}}==
 
−
HAA: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>A</u>'''clarubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5c5c2e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(13)70152-9 Jin et al. 2013]
 
−
| rowspan="2" |2007-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#7.2B3d_.28standard-dose.29|DA]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|2. [[#HAD|HAD]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Omacetaxine (Synribo)]] 2 mg/m<sup>2</sup>/day (route not specified) on days 1 to 7
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 7
 
−
*[[Aclarubicin (Aclacinon)]] 20 mg IV once per day on days 1 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patient in CR: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2
 
−
</div></div>
 
−
===References===
 
−
#Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://doi.org/10.1016/S1470-2045(13)70152-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23664707 PubMed] ChiCTR-TRC-06000054
 
−
==ICL {{#subobject:a904d7|Regimen=1}}==
 
−
ICL: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>L</u>'''omustine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:909d7e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.78.7366 Pigneux et al. 2017 (LAM-SA 2007)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#7.2B3i|IA]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS24: 56% vs 48%<br>(HR 0.73, 95% CI 0.54-0.99)
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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>)
 
−
*[[Lomustine (CCNU)]] 200 mg/m<sup>2</sup> PO once on day 1
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Acute_myeloid_leukemia#IC_.26_Norethandrolone|IC and methotrexate/mercaptopurine with norethandrolone]]
 
−
</div></div>
 
−
===References===
 
−
#'''LAM-SA 2007:''' Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. [https://doi.org/10.1200/JCO.2018.78.7366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30260758 PubMed] NCT00590837
 
−
==MEC {{#subobject:324735|Regimen=1}}==
 
−
MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
 
−
<br>MICE: '''<u>MI</u>'''toxantrone, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 
−
<br>MAE: '''<u>M</u>'''itoxantrone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:33e408|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895135/ Amadori et al. 2005 (EORTC/GIMEMA AML-13)]
 
−
|1995-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MEC_.26_G-CSF_88|MICE & G-CSF]]
 
−
| style="background-color:#d73027" |Inferior CR rate
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.49.0771 Amadori et al. 2013 (EORTC/GIMEMA AML-17)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Gemtuzumab_ozogamicin_monotherapy_99|GO]], then [[#MEC|MICE]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 10 vs 7.1 mo<br>(HR 0.83, 95% CI 0.69-1.01)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 
−
'''7-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''EORTC/GIMEMA AML-13:''' Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. [http://www.bloodjournal.org/content/106/1/27.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895135/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15761020 PubMed] NCT00002719
 
−
##'''Update:''' Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. [https://www.nature.com/articles/2404356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16932345 PubMed]
 
−
#'''EORTC/GIMEMA AML-17:''' Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. [https://doi.org/10.1200/JCO.2013.49.0771 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24127442 PubMed] NCT00052299
 
−
=Subsequent induction therapy, standard and older "fit" patients=
 
−
''Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.''
 
−
==DA 3+8 {{#subobject:5c6662|Regimen=1}}==
 
−
DA 3+8: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:aq1641|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)]]
 
−
|[[#DA_3.2B8_.26_Everolimus_99|DA 3+8 & Everolimus]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2
 
−
</div></div>
 
−
===References===
 
−
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
 
−
##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed]
 
−
==DA 3+8 & GO {{#subobject:6yy4bz|Regimen=1}}==
 
−
DA 3+8 & GO: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 8</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6a51fv|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2011-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Core-binding factor (CBF) AML
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2
 
−
</div></div>
 
−
===References===
 
−
#'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
 
−
##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed]
 
−
=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 {{#subobject:791718|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7509ab|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.23.8329 Fenaux et al. 2009 (AZA PH GL 2003)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|Investigator's choice of:<br> 1. [[Acute_myeloid_leukemia_-_null_regimens#Best_supportive_care|Best supportive care]]<br> 2. [[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]<br> 3. [[Regimen_classes#Intensive_chemotherapy|Intensive chemotherapy]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 24.5 vs 16 mo<br>(HR 0.47, 95% CI 0.28-0.79)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|Investigator's choice of:<br> 1. [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose<br> 2. [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose<br> 3. [[#7.2B3i|7+3i]]<br> 4. [[Acute_myeloid_leukemia_-_null_regimens#Best_supportive_care|Best supportive care]]<br> 5. [[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 10.4 vs 6.5 mo<br>(HR 0.85, 95% CI 0.69-1.03)
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.33403 Vives et al. 2021 (FLUGAZA)]
 
−
|2014-NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#FLUGA_88|FLUGA]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 9.8 vs 4.1 mo
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2012971 DiNardo et al. 2020 (VIALE-A)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Azacitidine_.26_Venetoclax|Azacitidine & Venetoclax]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
 
−
'''28-day cycle for at least 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''AZA PH GL 2003:''' Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. [https://doi.org/10.1200/JCO.2009.23.8329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20026804 PubMed] NCT00071799
 
−
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 
−
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 
−
#'''VIALE-A:''' DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. [https://doi.org/10.1056/nejmoa2012971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32786187 PubMed] NCT02993523
 
−
#'''FLUGAZA:''' Vives S, Martínez-Cuadrón D, Bergua Burgues J, Algarra L, Tormo M, Martínez-Sánchez MP, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, López-Lorenzo JL, Gil C, Vidriales B, Falantes JF, Serrano A, Labrador J, Sayas MJ, Foncillas MÁ, Amador Barciela ML, Olave MT, Colorado M, Gascón A, Fernández MÁ, Simiele A, Pérez-Encinas MM, Rodríguez-Veiga R, García O, Martínez-López J, Barragán E, Paiva B, Sanz MÁ, Montesinos P; PETHEMA Group. A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia. Cancer. 2021 Jun 15;127(12):2003-2014. Epub 2021 Feb 24. [https://doi.org/10.1002/cncr.33403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33626197/ PubMed] NCT02319135
 
−
# '''PEVOLAM:''' NCT04090736
 
−
# '''PRAN-16-52:''' NCT03151408
 
−
==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1ea50d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(18)30010-x DiNardo et al. 2018 (M14-358)]
 
−
|2014-2015
 
−
| style="background-color:#91cf61" |Phase 1b, >20 pts (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2012971 DiNardo et al. 2020 (VIALE-A)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Azacitidine_monotherapy|Azacitidine]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 14.7 vs 9.6 mo<br>(HR 0.66, 95% CI 0.52-0.85)
 
−
|-
 
−
|}
 
−
''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 
−
====Targeted therapy====
 
−
*[[Venetoclax (Venclexta)]] as follows:
 
−
**Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28
 
−
**Cycle 2 onwards: 400 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773]
 
−
##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed]
 
−
#'''VIALE-A:''' DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. [https://doi.org/10.1056/nejmoa2012971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32786187 PubMed] NCT02993523
 
−
#'''ENHANCE-2:''' NCT04778397
 
−
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:188f5c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1080/10428190802451254 Nand et al. 2008]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
 
−
|2008-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.''
 
−
====Supportive therapy, pre-treatment phase====
 
−
*[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or in higher doses if necessary
 
−
''Once WBC is less than 10 x 10<sup>9</sup>/L, stop Hydrea and proceed:''
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
 
−
====Supportive therapy====
 
−
*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====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_.26_Gemtuzumab_ozogamicin_2|Azacitidine and gemtuzumab ozogamicin]] consolidation, within 60 days
 
−
</div></div>
 
−
===References===
 
−
#Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [https://doi.org/10.1080/10428190802451254 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19021057 PubMed]
 
−
<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
 
−
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 
−
==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20 mg/m<sup>2</sup> {{#subobject:42be8e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.42.2964 Burnett et al. 2012 (UK NCRI AML16)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2013 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''4- to 6-week cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f9ef00|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.26.4242 Burnett et al. 2010 (UWCM-001)]
 
−
|2003-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ Faderl et al. 2008 (MDACC 2004-0183)]
 
−
|2004-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.26.4242 Burnett et al. 2010 (BIOV-121)]
 
−
|2004-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''5-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*A second induction was permitted for SD or better.
 
−
*MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218
 
−
#'''UWCM-001; BIOV-121:''' Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. [https://doi.org/10.1200/JCO.2009.26.4242 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20385984 PubMed]
 
−
#'''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. [https://doi.org/10.1200/jco.2012.42.2964 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22851554 PubMed] ISRCTN11036523
 
−
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 
−
==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}==
 
−
Clofarabine & LoDAC: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:12351c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ Faderl et al. 2008 (MDACC 2004-0183)]
 
−
|2004-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Clofarabine_monotherapy|Clofarabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
'''28- to 49-day cycle for up to 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CRi or better: [[#Clofarabine_.26_LoDAC_2|Clofarabine & LoDAC]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:7d207f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ Faderl et al. 2010]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients not achieving CR: Optional identical [[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]] re-induction after at least 28 days
 
−
**Patients not achieving CR after the second induction: [[#Decitabine_monotherapy_3|Decitabine]] salvage
 
−
*Patients achieving CR: [[#Clofarabine_.26_LoDAC.2FDecitabine|Clofarabine & low-dose cytarabine alternating with decitabine]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218
 
−
#Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed]
 
−
##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed]
 
−
==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}==
 
−
CPX-351: Liposomal Cytarabine and Daunorubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0b4cdf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ Lancet et al. 2014 (CLTR0308-204)]
 
−
|2008-2009
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ Lancet et al. 2018 (CLTR0310-301)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
 
−
| style="background-color:#1a9851" |Superior OS<sup>1</sup><br>Median OS: 9.3 vs 6.0 mo<br>(HR 0.70, 95% CI 0.55-0.91)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
**Second induction (if needed): 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3
 
−
'''One or two courses'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CR/CRi: [[#CPX-351_monotherapy_2|CPX-351]] consolidation
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, FL December 4-7, 2010. -->
 
−
#'''CLTR0308-204:''' Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. [http://www.bloodjournal.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687088 PubMed] NCT00788892
 
−
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 
−
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 
−
##'''Update:''' Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. [https://doi.org/10.1016/s2352-3026(21)00134-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34171279/ PubMed]
 
−
==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:b60a91|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ Issa et al. 2014]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[Acute_myeloid_leukemia_-_historical#Decitabine_.26_Valproate|Decitabine & Valproate]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''4- to 6-week cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:22a24e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ Kantarjian et al. 2012 (DACO-016)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]<br> 2. [[Acute_myeloid_leukemia_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 7.7 vs 5 mo<br>(HR 0.85, 95% CI 0.69-1.04)
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.33828 Kantarjian et al. 2021 (SEAMLESS)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Decitabine.2FSapacitabine_77|Decitabine/Sapacitabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787975/ Montesinos et al. 2020 (JNJ AML2002)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Decitabine_.26_Talacotuzumab_77|Decitabine & Talacotuzumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of CR/OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Hydroxyurea (Hydrea)]] (dose not specified) could be used up until cycle 1 day 15
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:c6ffdd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ Blum et al. 2010 (OSU 07017)]
 
−
|2007-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217532/ Welch et al. 2016 (Wash U 201210102)]
 
−
|2013-2015
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 10
 
−
====Supportive therapy====
 
−
*[[Hydroxyurea (Hydrea)]] (dose not specified) allowed during and prior to cycle 1
 
−
'''28-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above
 
−
*OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401
 
−
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
 
−
#'''DACO-016:''' Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.38.9429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689805 PubMed] NCT00260832
 
−
##'''Subgroup analysis:''' Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. [https://doi.org/full/10.1002/ajh.25062 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29417613 PubMed]
 
−
#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://doi.org/10.1002/cncr.29085 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25336333 PubMed]
 
−
#'''Wash U 201210102:''' Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon D, Lee Y, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036. [https://doi.org/10.1056/NEJMoa1605949 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217532/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27959731 PubMed] NCT01687400
 
−
#'''JNJ AML-2002:''' Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. [https://doi.org/10.1038/s41375-020-0773-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787975/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32203138 PubMed] NCT02472145
 
−
#'''SEAMLESS:''' Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. [https://doi.org/10.1002/cncr.33828 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34424530/ PubMed] NCT01303796
 
−
==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 5 days of decitabine {{#subobject:2aab30|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(18)30010-x DiNardo et al. 2018 (M14-358)]
 
−
|2014-2015
 
−
| style="background-color:#91cf61" |Phase 1b, >20 pts (RT)
 
−
|-
 
−
|}
 
−
''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
 
−
====Chemotherapy====
 
−
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 10 days of decitabine {{#subobject:08cde2|Variant=2}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7549397/ DiNardo et al. 2020 (DEC10-VEN)]
 
−
|2018-2019
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m<sup>2</sup> was allowed during cycle 1.''
 
−
====Chemotherapy====
 
−
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 10
 
−
====Targeted therapy====
 
−
*[[Venetoclax (Venclexta)]] as follows:
 
−
**Cycle 1: 400 mg PO once per day
 
−
**Cycle 2 onwards: 400 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773]
 
−
##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed]
 
−
<!-- #'''Abstract:''' Maiti A, DiNardo CD, Cortes JE, Borthakur G, Pemmaraju,N, Benton CB, Kadia TM, Takahashi K, Naqvi K, Ravandi F, Alvarado Y, Short NJ, Daver NG, Sasaki K, Ohanian MN, Garcia-Manero G, Thompson PA, Kornblau SM, Masarova L, Jain N, Jabbour EJ, Andreeff M, Maduike R, Guerrero JA, Zhang Q, Cavazos A, Ma H, Rausch CR, Bivins CA, Vaughan K, Pierce SA, Ning J, Qiao W, Welch JS, Kantarjian HM,  Konopleva MY. Interim Analysis of Phase II Study of Venetoclax with 10-Day Decitabine (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Blood, 132(Suppl 1), 286. [http://www.bloodjournal.org/content/132/Suppl_1/286 link to original abstract] [https://clinicaltrials.gov/ct2/show/NCT03404193 NCT03404193] -->
 
−
#'''DEC10-VEN:''' DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. [https://doi.org/10.1016/s2352-3026(20)30210-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7549397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32896301 PubMed] NCT03404193
 
−
==Gemtuzumab ozogamicin monotherapy {{#subobject:4e3c9a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e01685|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2015.64.0060 Amadori et al. 2016 (EORTC/GIMEMA AML-19)]
 
−
|2004-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Acute_myeloid_leukemia_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 4.9 vs 3.6 mo<br>(HR 0.69, 95% CI 0.53-0.90)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV once on day 1, then 3 mg/m<sup>2</sup> IV once on day 8
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin]] maintenance
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
−
#'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234
 
−
==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}==
 
−
Glasdegib & LoDAC: Glasdegib & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e4c7c9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ Cortes et al. 2018 (BRIGHT AML 1003)]
 
−
|2014-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-esc)
 
−
|[[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 8.3 vs 4.3 mo<br>(HR 0.495, 95% CI 0.325-0.75)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10
 
−
====Targeted therapy====
 
−
*[[Glasdegib (Daurismo)]] 100 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Cortes JE, Heidel FH, Heuser M, Fiedler W, Smith BD, Robak T. Montesinos Fernandez P, Ma WW, Shaik MN, Zeremski M, O'Connell A,  Chan, G. A Phase 2 Randomized Study of Low Dose Ara-C with or without Glasdegib (PF-04449913) in Untreated Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. Blood 2016, 128(22), 99. [http://www.bloodjournal.org/content/128/22/99 link to original article] '''contains dosing details in manuscript''' -->
 
−
#'''BRIGHT AML 1003:''' Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. [https://www.nature.com/articles/s41375-018-0312-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30555165 PubMed] NCT01546038
 
−
##'''Update:''' Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. [https://doi.org/10.1007/s00277-021-04465-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8043884/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33740113/ PubMed]
 
−
==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:25e1c6|Regimen=1}}==
 
−
LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<br>LDAC: '''<u>L</u>'''ow-dose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20 mg twice per day, indefinite duration {{#subobject:a3d4fb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132839/ Kantarjian et al. 2013 (SPARK-AML1)]
 
−
|2009-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Barasertib_.26_LoDAC_77|Barasertib & LoDAC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OCRR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148765/ Döhner et al. 2014 (BI 1230.4)]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#LoDAC_.26_Volasertib_77|LoDAC & Volasertib]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ Cortes et al. 2018 (BRIGHT AML 1003)]
 
−
|2014-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Glasdegib_.26_LoDAC|Glasdegib & LoDAC]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 20 mg/m<sup>2</sup> twice per day, limited duration {{#subobject:d5c6f7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.42.2964 Burnett et al. 2012 (UK NCRI AML16)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Clofarabine_monotherapy|Clofarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533673/ Sekeres et al. 2012 (SG033-0003)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#LoDAC_.26_Lintuzumab_77|LoDAC & Lintuzumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2015.38 Burnett et al. 2015]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Sapacitabine_monotherapy_77|Sapacitabine]]
 
−
| style="background-color:#fee08b" |Might have inferior CR rate
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Azacitidine_monotherapy|Azacitidine]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ Dennis et al. 2015 (UK NCRI LI-1)]
 
−
| rowspan="2" |2012-2013
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#LoDAC_.26_Vosaroxin_77|LDAC & Vosaroxin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR/CRi rate
 
−
|-
 
−
|2. [[#Vosaroxin_monotherapy_77|Vosaroxin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR/CRi rate
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for UK NCRI AML16 is based on the 2016 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10
 
−
'''4- to 6-week cycle for up to 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 20 mg/m<sup>2</sup> once per day, indefinite duration {{#subobject:fd61d0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ Kantarjian et al. 2012 (DACO-016)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Decitabine_monotherapy|Decitabine]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ Wei et al. 2020 (VIALE-C)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#LoDAC_.26_Venetoclax|LoDAC & Venetoclax]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
 
−
#'''DACO-016:''' Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.38.9429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689805 PubMed] NCT00260832
 
−
##'''Subgroup analysis:''' Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. [https://doi.org/full/10.1002/ajh.25062 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29417613 PubMed]
 
−
#'''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://pubmed.ncbi.nlm.nih.gov/22801961 PubMed] NCT00528333
 
−
#'''UK NCRI AML16:''' Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. [https://doi.org/10.1200/jco.2012.42.2964 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22851554 PubMed] ISRCTN11036523
 
−
##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 
−
#'''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://doi.org/full/10.1002/cncr.28113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132839/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23605952 PubMed] NCT00952588
 
−
#'''BI 1230.4:''' Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Müller-Tidow C, Krämer A, Raffoux E, Döhner K, Schlenk RF, Voss F, Taube T, Fritsch H, Maertens J. Randomized, phase 2 trial comparing low-dose cytarabine with or without volasertib in AML patients not suitable for intensive induction therapy. Blood. 2014 Aug 28;124(9):1426-33. Epub 2014 Jul 8. [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://pubmed.ncbi.nlm.nih.gov/25006120 PubMed] NCT00804856
 
−
# Burnett AK, Russell N, Hills RK, Panoskaltsis N, Khwaja A, Hemmaway C, Cahalin P, Clark RE, Milligan D. A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia. Leukemia. 2015 Jun;29(6):1312-9. Epub 2015 Feb 13. [https://doi.org/10.1038/leu.2015.38 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25676423 PubMed]
 
−
#'''UK NCRI LI-1:''' Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood. 2015 May 7;125(19):2923-32. Epub 2015 Mar 24. [http://www.bloodjournal.org/content/125/19/2923.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25805811 PubMed] ISRCTN40571019
 
−
#'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 
−
##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 
−
#'''BRIGHT AML 1003:''' Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. [https://www.nature.com/articles/s41375-018-0312-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30555165 PubMed] NCT01546038
 
−
##'''Update:''' Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. [https://doi.org/10.1007/s00277-021-04465-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8043884/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33740113/ PubMed]
 
−
#'''VIALE-C:''' Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. [https://doi.org/10.1182/blood.2020004856 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32219442 PubMed] NCT03069352
 
−
##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed]
 
−
#'''POLO-AML-2:''' NCT01721876
 
−
==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}==
 
−
LoDAC & Venetoclax: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & Venetoclax
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e84ab4|Variant=1}}===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524989/ Wei et. al. 2019 (M14-387)]
 
−
|2015-2017
 
−
| style="background-color:#91cf61" |Phase 1b/2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ Wei et al. 2020 (VIALE-C)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Low-dose_Cytarabine_monotherapy_.28LoDAC.29|LoDAC]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 8.4 vs 4.1 mo<br>(HR 0.70, 95% CI 0.50-0.99)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for VIALE-C is based on the 2021 update.''<br>
 
−
''The dose of venetoclax in M14-387 was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors.''
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10
 
−
====Targeted therapy====
 
−
*[[Venetoclax (Venclexta)]] as follows:
 
−
**Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28
 
−
**Cycle 2 onwards: 600 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''M14-387:''' Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. [https://doi.org/10.1200/JCO.18.01600 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524989/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30892988 PubMed] NCT02287233
 
−
#'''VIALE-C:''' Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. [https://doi.org/10.1182/blood.2020004856 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32219442 PubMed] NCT03069352
 
−
##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed]
 
−
==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fb4aeb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13094 Brandwein et al. 2014]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Patient selection was based on MGMT expression by Western blot. See article for details.''
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''28-day cycle for up to 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. [https://doi.org/10.1111/bjh.13094 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25160658 PubMed]
 
−
=Consolidation after upfront therapy=
 
−
==5+2d {{#subobject:b409f7|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a67da7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ Lancet et al. 2018 (CLTR0310-301)]
 
−
|2012-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''5-day course'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 
−
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 
−
==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:caa3a2|Regimen=1}}==
 
−
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<br>HDAC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<br>HDAraC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>AraC</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:4e73ae|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.37.1286 Holowiecki et al. 2012 (PALG AML1/2004)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Details in the text are scant.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cytarabine_.26_Mitoxantrone_.28MC.29|Cytarabine & Mitoxantrone]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m<sup>2</sup>)
 
−
'''5-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:2a4b32|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 17%" |Study
 
−
! style="width: 15%" |Years of enrollment
 
−
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 17%" |Comparator
 
−
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/32/2/643.long Fukushima et al. 2012]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Randomized, <20 pts in this arm (C)
 
−
|[[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|mIDAC]]
 
−
|
 
−
| style="background-color:#fc8d59" |Seems to be more toxic
 
−
|-
 
−
|}
 
−
''Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BHAC-MMV_88|BHAC-MMV]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*A-VVV
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1 cycle of 3000 mg/m<sup>2</sup> every 12 hours x 12 {{#subobject:a0e7d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199812033392301 Cassileth et al. 1998]
 
−
|1990-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#BuCy.2C_then_auto_HSCT|BuCy, then auto HSCT]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#5.2B2i_88|5+2i]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>)
 
−
'''6-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 3 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:746f61|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ Moore et al. 2004 (CALGB 9222)]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]], then [[#CYVE|CYVE]], then [[#Diaziquone_.26_Mitoxantrone_77|AZQ & Mitoxantrone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.46.4743 Schaich et al. 2013 (AML2003)]
 
−
|2003-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MAC.2FMAMAC.2FMAC_99|MAC/MAMAC/MAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ Petersdorf et al. 2013 (SWOG S0106)]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2014.57.0952 Stone et al. 2015 (ACCEDE)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00362-9 Röllig et al. 2015 (SORAML)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#HiDAC_.26_Sorafenib_88|HiDAC & Sorafenib]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.8618 Stone et al. 2015 (COSAH C-022)]
 
−
|2010-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*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]]
 
−
*AML2003: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose x 2
 
−
*ACCEDE: [[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]] versus [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
*SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]]
 
−
*COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
−
'''3 cycles of varying durations'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SWOG S0106: GO maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 3 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:8887b8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/117/8/2358 Ohtake et al. 2010 (JALSG AML201)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|Multiagent chemotherapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B5d_88|7+5d]] or [[#7.2B3i|7+3i]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>)
 
−
'''3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10<sup>9</sup>/L, and 100 × 10<sup>9</sup>/L'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 4 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:0c2779|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199410063311402 Mayer et al. 1994 (CALGB 8525)]
 
−
|1985-1990
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cytarabine_monotherapy_88|Low-dose continuous infusion cytarabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/7/1754.long Thomas et al. 2011 (ALFA-9802)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Timed sequential chemotherapy (TSC)
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
 
−
|2010-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*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]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for up to 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ALFA-9802: Cytarabine & Daunorubicin maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''CALGB 8525:''' Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; [[Study_Groups#CALGB|CALGB]]. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://doi.org/10.1056/NEJM199410063311402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8078551 PubMed]
 
−
#Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. [https://doi.org/10.1056/NEJM199812033392301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9834301 PubMed]
 
−
#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15572587 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://pubmed.ncbi.nlm.nih.gov/20693429 PubMed] C000000157
 
−
##'''Update:''' Miyawaki S, Ohtake S, Fujisawa S, Kiyoi H, Shinagawa K, Usui N, Sakura T, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2366-72. Epub 2010 Dec 29. [http://www.bloodjournal.org/content/117/8/2366.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21190996 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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21690555 PubMed] NCT00880243
 
−
#Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22287757 PubMed]
 
−
#'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709
 
−
#'''AML2003:''' Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. [https://doi.org/10.1200/JCO.2012.46.4743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23630210 PubMed] NCT00180102
 
−
#'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637
 
−
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 
−
#'''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://doi.org/10.1016/S1470-2045(15)00362-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26549589 PubMed] NCT00893373
 
−
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 
−
==Intermediate-dose Cytarabine monotherapy (IDAC) {{#subobject:f5cd74|Regimen=1}}==
 
−
IDAC: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<br>mIDAC: '''<u>m</u>'''odified '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1000 mg/m<sup>2</sup> x 3 {{#subobject:0340ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2014.57.0952 Stone et al. 2015 (ACCEDE)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]] versus [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
'''3 cycles (length not specified)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1000 mg/m<sup>2</sup> x 10 {{#subobject:cbba35|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 17%" |Study
 
−
! style="width: 15%" |Years of enrollment
 
−
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 17%" |Comparator
 
−
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/32/2/643.long Fukushima et al. 2012]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Randomized, <20 pts in this arm (E-de-esc)
 
−
|[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HDAC]]
 
−
|
 
−
| style="background-color:#91cf60" |Seems to be less toxic
 
−
|-
 
−
|}
 
−
''Note: cycle length was not specified; 28-day cycles are frequently used in this setting.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BHAC-MMV_88|BHAC-MMV]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for 2 cycles (see note)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*A-VVV
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1000 mg/m<sup>2</sup> x 12 {{#subobject:22eda3|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
 
−
|2000-2006
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose versus [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m<sup>2</sup>)
 
−
'''6-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Transplant eligible patients: [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]]
 
−
*Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]]
 
−
</div></div>
 
−
===References===
 
−
#'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377
 
−
#Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22287757 PubMed]
 
−
#'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637
 
−
==HiDAC & G-CSF {{#subobject:e0396d|Regimen=1}}==
 
−
HiDAC & G-CSF: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & '''<u>G</u>'''ranulocyte '''<u>C</u>'''olony '''<u>S</u>'''timulating '''<u>F</u>'''actor
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d8edc4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.70.4551 Thomas et al. 2017 (ALFA-0702)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#CLARA|CLARA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 5
 
−
'''35-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412
 
−
==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f7e3f6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
 
−
|2008-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once on day 1
 
−
'''28-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===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). -->
 
−
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 
−
==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:eb3f69|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
 
−
|2008-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
 
−
====Supportive therapy====
 
−
*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
 
−
*Growth factors per physician discretion
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Azacitidine_monotherapy_2|Azacitidine]] maintenance, within 42 days of completion of consolidation
 
−
</div></div>
 
−
===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). -->
 
−
#'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 
−
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
 
−
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6ccf66|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/23/6037.long Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)]
 
−
|1995-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Etoposide_.26_Mitoxantrone|Etoposide & Mitoxantrone]]
 
−
| style="background-color:#d9ef8b" |Might have superior RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_.88|Amsacrine & Cytarabine]]
 
−
{{#lst:Autologous HSCT|6ccf66}}
 
−
</div></div>
 
−
===References===
 
−
#'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed]
 
−
==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}==
 
−
BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a7e574|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ Devine et al. 2015 (CALGB 100103)]
 
−
|2004-2011
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in subgroup
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
 
−
|2008-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|a7e574}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===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. -->
 
−
#'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135
 
−
==CIA {{#subobject:db5c09|Regimen=1}}==
 
−
CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1bbed8|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ Nazha et al. 2013]
 
−
|2010-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#CIA|CIA]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity'''
 
−
</div></div>
 
−
===References===
 
−
#Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed]
 
−
==CLARA {{#subobject:6160cf|Regimen=1}}==
 
−
CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6ed739|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.70.4551 Thomas et al. 2017 (ALFA-0702)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#HiDAC_.26_G-CSF|HiDAC & G-CSF]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 6
 
−
'''35-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412
 
−
==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}==
 
−
Clofarabine & LoDAC/Decitabine: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) alternating with Decitabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:0ac883|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ Faderl et al. 2010]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====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.
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, clofarabine & LoDAC portion====
 
−
*[[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
 
−
*[[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/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''4- to 7-week cycles, depending on count recovery'''
 
−
</div></div>
 
−
===References===
 
−
#Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed]
 
−
##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed]
 
−
==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}==
 
−
CPX-351: Liposomal Cytarabine and Daunorubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:896083|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ Lancet et al. 2018 (CLTR0310-301)]
 
−
|2012-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#CPX-351_monotherapy|CPX-351]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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
 
−
'''5- to 8-week cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 
−
#'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 
−
==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:c39b55|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)60485-1 Castaigne et al. 2012 (ALFA-0701)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10<sup>9</sup> at day 45 from initiation of chemotherapy were assigned to this regimen.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose or [[#7.2B3d_.26_GO|7+3d & GO]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] as follows:
 
−
**Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''2 cycles (length not specified)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:59874e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/109/12/5129.full Gardin et al. 2007 (ALFA 9803)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#4d_.2B_7_88|4d + 7]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B4d_88|4d + 7]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once on day 1
 
−
'''1-month cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025
 
−
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 
−
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 
−
==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c56261|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)60485-1 Castaigne et al. 2012 (ALFA-0701)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.26_GO|7+3d & GO]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] as follows:
 
−
**Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once on day 1
 
−
'''2 cycles (length not specified)'''
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 
−
##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 
−
==CYVE {{#subobject:f8d436|Regimen=1}}==
 
−
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:79438d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
 
−
|2010-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: this consolidation regimen was for patients with high-risk cytogenetics.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]]
 
−
<div class="toccolours" style="width:100%; overflow:auto;">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''4 courses'''
 
−
</div>
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Transplant eligible patients with available donors usually proceeded to [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] after 2 courses (details not specified)
 
−
</div></div>
 
−
===References===
 
−
#'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 
−
==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:099908|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/109/12/5129.full Gardin et al. 2007 (ALFA 9803)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#4i_.2B_7_88|4i + 7]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B4i_88|4i + 7]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>)
 
−
*[[Idarubicin (Idamycin)]] 9 mg/m<sup>2</sup> IV once on day 1
 
−
'''1-month cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025
 
−
==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:97a478|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010 (BAY43-9006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
''Regimen details are from the phase 2 part of the published phase 1/2 trial.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day for up to 28 days
 
−
'''4- to 6-week cycle for up to 5 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Sorafenib_monotherapy|Sorafenib]] maintenance
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 
−
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 
−
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==
 
−
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6ca28d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198005083021901 Blume et al. 1980]
 
−
|1976-1979
 
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199501263320403 Zittoun et al. 1995]
 
−
|1986-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Regimen_classes#Intensive_chemotherapy|Intensive chemotherapy]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70349-2 Bornhäuser et al. 2012 (9005-2003)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fludarabine_.26_TBI.2C_then_allo_HSCT|Fludarabine & TBI, then allo HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary efficacy endpoints
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of NRM
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then [[Stub#Amsacrine_.26_IDAC|Amsacrine & IDAC]]
 
−
{{#lst:Allogeneic HSCT|6ca28d}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https://doi.org/10.1056/NEJM198005083021901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6245359 PubMed]
 
−
#Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https://doi.org/10.1056/NEJM199501263320403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7808487 PubMed]
 
−
#'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878
 
−
#'''Retrospective:''' Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. [http://www.bloodjournal.org/content/122/24/3863.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854108/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24065243 PubMed]
 
−
==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}==
 
−
ME: '''<u>M</u>'''itoxantrone & '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3 days {{#subobject:78ghc3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (AMLSG31-19)
 
−
|2021-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Etoposide_.26_Mitoxantrone_.28ME.29_.26_Venetoclax_88|ME & Venetoclax]]
 
−
| style="background-color:#d3d3d3" |In progress
 
−
|-
 
−
|}
 
−
''Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28intermediate-dose.29|7+3d]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''One course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5 days {{#subobject:780933|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/23/6037.long Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)]
 
−
|1995-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#BuCy.2C_then_auto_HSCT|Bu/Cy, then auto HSCT]]
 
−
| style="background-color:#fee08b" |Might have inferior RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''One course'''
 
−
</div></div>
 
−
===References===
 
−
#'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed]
 
−
#'''AMLSG31-19:''' NCT04628026
 
−
==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:be3609|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70349-2 Bornhäuser et al. 2012 (9005-2003)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_TBI.2C_then_allo_HSCT|Cyclophosphamide & TBI, then allo HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary efficacy endpoints
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of NRM
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|be3609}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ Gyukocza et al. 2010]
 
−
|1998-2008
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|7fa6ce}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed]
 
−
#'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878
 
−
==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dd1486|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ Devine et al. 2015 (CALGB 100103)]
 
−
|2004-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|dd1486}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===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. -->
 
−
#'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135
 
−
==HAM {{#subobject:1da5a5|Regimen=1}}==
 
−
HAM: '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:eb86c6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1600-0609.2007.00988.x Wierzbowksa et al. 2007]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.37.1286 Holowiecki et al. 2012 (PALG AML1/2004)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Wierzbowska et al. 2007: [[#CLAG-M|CLAG-M]]
 
−
*PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus [[#DAF_99|DAF]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
#'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 
−
==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}==
 
−
IC & Norethandrolone: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, Norethandrolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:0849b9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.67.6213 Pigneux et al. 2016 (GOELAMS LAM-SA2002)]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#IC.2FMercaptopurine_.26_Methotrexate_88|IC/6-MP & MTX]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ICL|7+3i & Lomustine]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, reinduction====
 
−
*[[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>)
 
−
====Endocrince therapy, reinduction====
 
−
*[[Norethandrolone (Nilevar)]] by the following weight-based criteria:
 
−
**If less than 60 kg: 10 mg PO once per day
 
−
**If greater than 60 kg: 20 mg PO once per day
 
−
'''3-month cycle for 6 cycles, alternating with maintenance'''
 
−
====Chemotherapy, maintenance====
 
−
*[[Methotrexate (MTX)]] by the following weight-based criteria:
 
−
**If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11
 
−
**If greater than 60 kg: 25 mg PO once per day on days 1, 4, 8, 11
 
−
*[[Mercaptopurine (6-MP)]] by the following weight-based criteria:
 
−
**If less than 60 kg: 100 mg PO once per day on days 15 to 30
 
−
**If greater than 60 kg: 150 mg PO once per day on days 15 to 30
 
−
====Endocrine therapy, maintenance====
 
−
*[[Norethandrolone (Nilevar)]] by the following weight-based criteria:
 
−
**If less than 60 kg: 10 mg PO once per day
 
−
**If greater than 60 kg: 20 mg PO once per day
 
−
'''3-month cycle for 6 cycles, alternating with re-induction courses'''
 
−
</div></div>
 
−
===References===
 
−
#'''GOELAMS LAM-SA2002:''' Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. [https://doi.org/10.1200/JCO.2016.67.6213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129526 PubMed] NCT00700544
 
−
==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}==
 
−
TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:174a8e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ Gyukocza et al. 2010]
 
−
|1998-2008
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|174a8e}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed]
 
−
=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 {{#subobject:887fd6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 12 cycles {{#subobject:482f12|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2018-10-879866 Huls et al. 2019 (HOVON97)]
 
−
|2009-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Acute_myeloid_leukemia_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS<br>DFS12: 64% vs 42%<br>(aHR 0.62, 95% CI 0.41-0.95)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*At least 2 cycles of [[Regimen_classes#Intensive_chemotherapy|intensive chemotherapy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 50 mg/m<sup>2</sup> SC once per day on days 1 to 5
 
−
'''28-day cycle for up to 12 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:482f11|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2010.08235.x Grövdal et al. 2010]
 
−
|2004-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Intended to be used for transformed MDS patients in remission after AML induction therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B2d_88|7+2d]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. [https://doi.org/10.1111/j.1365-2141.2010.08235.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20497178 PubMed]
 
−
#'''HOVON97:''' Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. [https://doi.org/10.1182/blood-2018-10-879866 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30630862 PubMed] NTR1810
 
−
==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4726aa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ Blum et al. 2010 (OSU 07017)]
 
−
|2007-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Decitabine_monotherapy|Decitabine]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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.
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401
 
−
==Azacitidine oral monotherapy {{#subobject:da9efa|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:90f116|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2004444 Wei et al. 2020 (QUAZAR AML-001)]
 
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Acute_myeloid_leukemia_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 24.7 vs 14.8 mo
 
−
|-
 
−
|}
 
−
''<sup>1</sup>The proportional hazards assumption was violated, so hazard ratios are not reported.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Regimen_classes#Chemotherapy|Induction chemotherapy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine oral (Onureg)]] 300 mg PO once per day on days 1 to 14
 
−
'''28-day cycle'''
 
−
</div></div>
 
−
===References===
 
−
#'''QUAZAR AML-001:''' Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. [https://doi.org/10.1056/nejmoa2004444 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33369355 PubMed] NCT01757535
 
−
==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b7c813|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2015.64.0060 Amadori et al. 2016 (EORTC/GIMEMA AML-19)]
 
−
|2004-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin]] induction, with clinical benefit
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 2 mg/m<sup>2</sup> IV once on day 1
 
−
'''1-month cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 
−
#'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234
 
−
==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:4c65c8|Regimen=1}}==
 
−
LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
 
−
<br>LDAC: '''<u>L</u>'''ow '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2f5aa0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.nature.com/articles/2401850 Robles et al. 2000 (ECOG E5483)]
 
−
|1984-1988
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Acute_myeloid_leukemia_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_88|HiDAC]], then [[#Amsacrine_monotherapy_88|amsacrine]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 10 mg/m<sup>2</sup> SC twice per day on days 1 to 21
 
−
'''8-week cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ECOG E5483:''' Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. [https://www.nature.com/articles/2401850 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10942228 PubMed]
 
−
==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b50325|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010 (BAY43-9006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
 
−
'''Up to one year course, including consolidation'''
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 
−
##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 
−
=Relapsed or refractory, salvage therapy=
 
−
''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.''
 
−
==5+2d {{#subobject:df9bab|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c9d569|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ Zeidner et al. 2015 (JHOC-J1101)]
 
−
|2011-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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>)
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''5-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972
 
−
==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}==
 
−
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a99e51|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/12/4614.long Milligan et al. 2006 (MRC AML-HR)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#FLA|FLA]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Course 1: 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m<sup>2</sup>)
 
−
**Course 2: 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 8 (total dose: 1600 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''2 courses (length not specified)'''
 
−
</div></div>
 
−
===References===
 
−
#'''MRC AML-HR:''' Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. [http://www.bloodjournal.org/content/107/12/4614.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16484584 PubMed] NCT00005863
 
−
==CLAG {{#subobject:702383|Regimen=1}}==
 
−
CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:12d1bb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.3109/10428190009053545 Robak et al. 2000]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine)
 
−
</div></div>
 
−
===References===
 
−
#Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. [https://doi.org/10.3109/10428190009053545 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10975390 PubMed]
 
−
#'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed]
 
−
==CLAG-M {{#subobject:51b417|Regimen=1}}==
 
−
CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e0b308|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1600-0609.2007.00988.x Wierzbowksa et al. 2007]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] by the following criteria:
 
−
**WBC count less than or equal to 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 0 to 5, '''started 24 hours prior to chemotherapy'''
 
−
**WBC count greater than 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 1 to 5, '''started simultaneously to cladribine'''
 
−
'''6-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR were recommended to undergo a second course of [[#CLAG-M|CLAG-M]].
 
−
**Primary refractory patients achieving CR after 2nd CLAG-M: [[#HAM|HAM]] consolidation
 
−
*Others could receive another course of CLAG-M or [[#HAM|HAM]] consolidation per investigator discretion
 
−
</div></div>
 
−
===References===
 
−
#Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
#'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed]
 
−
==CLARA {{#subobject:48978a|Regimen=1}}==
 
−
CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
 
−
<br>GCLAC: '''<u>G</u>'''-CSF, '''<u>C</u>'''lofarabine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b8a3a2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ Becker et al. 2011 (UW 6562)]
 
−
|2007-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days
 
−
'''6-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with greater than 5% blasts at day 21: [[#CLARA_2|CLARA]] re-induction x 1
 
−
*Patients achieving CR: Optional [[#CLARA_3|CLARA]] consolidation for up to 2 cycles
 
−
</div></div>
 
−
===References===
 
−
#'''UW 6562:''' Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. [https://doi.org/10.1111/j.1365-2141.2011.08831.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21848522 PubMed] NCT00602225
 
−
==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20/20 variant 1 {{#subobject:d4a73c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13437 Buckley et al. 2015 (FHCRC 2302.00)]
 
−
|2009-2013
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10
 
−
'''Cycle duration not explicitly defined; presumably 28 days'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 20/20 variant 2 {{#subobject:dhg73c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13437 Buckley et al. 2015 (FHCRC 2302.00)]
 
−
|2009-2013
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 14
 
−
'''Cycle duration not explicitly defined; presumably 28 days'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 30/1000 {{#subobject:f6ada8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2015.226 Middeke et al. 2015 (BRIDGE)]
 
−
|2012-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''At least one cycle'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Chemo-responsive patients: [[#Clofarabine_.26_Melphalan.2C_then_allo_HSCT|Clofarabine & Melphalan, then allo HSCT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 40/1000 {{#subobject:d95457|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/3/940.long Faderl et al. 2004]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ Agura et al. 2011 (Baylor 004-145)]
 
−
|2005-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ Faderl et al. 2012 (CLASSIC I)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Acute_myeloid_leukemia_-_historical#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: length of cycles was not specified; 28-day cycle is typical for this regimen.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 3 to 4 hours after completion of clofarabine infusion'''
 
−
====Supportive therapy====
 
−
*Best described in Agura et al. 2011
 
−
*[[Dexamethasone (Decadron)]] 10 mg IV once per day
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]] on each day of chemotherapy
 
−
*Hydration at 150 mL/m<sup>2</sup>/H "to prevent tumor lysis syndrome" during chemotherapy
 
−
*[[Bumetanide (Bumex)]] 2 to 4 mg IV push once to twice per day as needed to keep weight within 1 kg of patient's initial weight
 
−
*[[Levofloxacin (Levaquin)]] 500 mg IV or PO once per day
 
−
*[[Acyclovir (Zovirax)]] 500 mg IV Q12H
 
−
*One of the following antifungals:
 
−
**[[Caspofungin (Cancidas)]] 50 mg IV once per day
 
−
**[[Voriconazole (Vfend)]] 200 mg (route not specified) twice per day
 
−
*Parenteral nutrition allowed
 
−
*No routine use of growth factors
 
−
'''28-day cycle for 1 to 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See individual papers for details
 
−
</div></div>
 
−
===References===
 
−
#Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. [http://www.bloodjournal.org/content/105/3/940.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15486072 PubMed]
 
−
#'''Baylor 004-145:''' Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. [http://theoncologist.alphamedpress.org/content/16/2/197.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21273514 PubMed] NCT00334074
 
−
<!-- 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. [https://doi.org/10.1200/jco.2011.37.9743 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22585697 PubMed] NCT00317642
 
−
#'''FHCRC 2302.00:''' Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25854284 PubMed]
 
−
#'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed]
 
−
==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7683cc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1988.6.2.213 Ho et al. 1988]
 
−
|1984-1987
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|ORR: 54%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
</div></div>
 
−
===References===
 
−
#Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. [https://doi.org/10.1200/jco.1988.6.2.213 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3422260 PubMed]
 
−
==FLAG {{#subobject:551761|Regimen=1}}==
 
−
FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9501d2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/(sici)1096-8652(199806)58:2%3C105::aid-ajh3%3E3.0.co;2-w Montillo et al. 1998]
 
−
|1994-1996
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
====Growth factor therapy====
 
−
*G-CSF with one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
 
−
**[[Lenograstim (Granocyte)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
 
−
'''6-day course'''
 
−
</div></div>
 
−
===References===
 
−
#Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. [https://doi.org/10.1002/(sici)1096-8652(199806)58:2%3C105::aid-ajh3%3E3.0.co;2-w link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9625576 PubMed]
 
−
==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}==
 
−
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Filgrastim), '''<u>Ida</u>'''rubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5fa1bb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1046/j.1365-2141.1997.4763281.x Parker et al. 1997]
 
−
|1995-1997
 
−
| style="background-color:#ffffbe" |Phase 2, <20 patients
 
−
|-
 
−
|[https://doi.org/10.1007/s00277-003-0624-2 Pastore et al. 2003]
 
−
|1998-2002
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery
 
−
'''5-day course'''
 
−
</div></div>
 
−
===References===
 
−
 
−
#Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. [https://doi.org/10.1046/j.1365-2141.1997.4763281.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432047 PubMed]
 
−
#Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. [https://doi.org/10.1007/s00277-003-0624-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12707726 PubMed]
 
−
==F-SHAI {{#subobject:9e1c5f|Regimen=1}}==
 
−
F-SHAI: '''<u>F</u>'''ludarabine, '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>I</u>'''darubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b50224|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2013.297 Fiegl et al. 2013]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Acute_myeloid_leukemia_-_historical#SHAI|SHAI]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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'''
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9
 
−
**Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
 
−
*[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL
 
−
**Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts
 
−
'''11-day course'''
 
−
</div></div>
 
−
===References===
 
−
#Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://doi.org/10.1038/leu.2013.297 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24150216 PubMed]
 
−
==Gemtuzumab ozogamicin monotherapy {{#subobject:4e1hba|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, fractionated dosing {{#subobject:jgaci5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.leu.2404434 Taksin et al. 2006 (MyloFrance-1)]
 
−
|2005
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 4, 7
 
−
'''One course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:e0aci5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.13.3244 Sievers et al. 2001]
 
−
|1997-1999
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
''Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 9 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [https://doi.org/10.1200/jco.2001.19.13.3244 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11432892 PubMed]
 
−
## '''Update:''' Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, Mineur P, Bennett JM, Berger MS, Eten CB, Munteanu M, Loken MR, Van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia. 2002 Sep;16(9):1627-36. [https://www.nature.com/articles/2402677 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12200674 PubMed]
 
−
## '''Update:''' Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. [https://doi.org/full/10.1002/cncr.21326 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16116598 PubMed]
 
−
#'''MyloFrance-1:''' Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. [https://doi.org/10.1038/sj.leu.2404434 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17051246/ PubMed]
 
−
==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:1dddf5|Regimen=1}}==
 
−
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, CI {{#subobject:e8a7af|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/114/19/4027.long Giles et al. 2009 (VION-CLI-037)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HiDAC_.26_Laromustine_77|HiDAC & Laromustine]]
 
−
| style="background-color:#ffffbf" |Mixed response (see note)
 
−
|-
 
−
|}
 
−
''Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m<sup>2</sup>)
 
−
'''3-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, intermittent {{#subobject:ab6f08|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0145-2126(99)00087-9 Karanes et al. 1999 (SWOG-8326)]
 
−
|1985-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HiDAC_.26_Mitoxantrone_99|HiDAC & Mitoxantrone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>)
 
−
'''6-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''SWOG-8326:''' Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. [https://doi.org/10.1016/s0145-2126(99)00087-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10475617 PubMed]
 
−
#'''VION-CLI-037:''' Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. [http://www.bloodjournal.org/content/114/19/4027.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19710500 PubMed] NCT00112554
 
−
==MAC {{#subobject:fba448|Regimen=1}}==
 
−
MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<br>MIDAC: '''<u>M</u>'''itoxantrone & '''<u>I</u>'''ntermediate-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6000/25 {{#subobject:5bf868|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/(sici)1097-0142(20000501)88:9%3C2037::aid-cncr8%3E3.0.co;2-k Sternberg et al. 2000]
 
−
|1990-1997
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 5 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m<sup>2</sup>)
 
−
'''6-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 10,000/48 {{#subobject:4a2f44|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/88/4/1198.long Solary et al. 1996]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cytarabine.2C_Mitoxantrone.2C_Quinine_99|Cytarabine, Mitoxantrone, Quinine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 2 to 5
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>)
 
−
'''5-day course'''
 
−
</div></div>
 
−
===References===
 
−
#Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. [http://www.bloodjournal.org/content/88/4/1198.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8695837 PubMed]
 
−
#Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. [https://doi.org/10.1002/(sici)1097-0142(20000501)88:9%3C2037::aid-cncr8%3E3.0.co;2-k link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10813714 PubMed]
 
−
==MEC {{#subobject:48e49b|Regimen=1}}==
 
−
MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6/80/1000 {{#subobject:ac3985|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1991.9.7.1210 Amadori et al. 1991]
 
−
|1988-1990
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 6
 
−
'''6-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 8/80/1000 {{#subobject:9ad362|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.09.133 Feldman et al. 2005]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MEC_.26_Lintuzumab_77|MEC & Lintuzumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6
 
−
'''6-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 8/100/1000 {{#subobject:bd7f87|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ Greenberg et al. 2004 (ECOG E2995)]
 
−
|NR-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MEC_.26_Valspodar_77|MEC & Valspodar]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ Cortes et al. 2014 (CLTR0308-205)]
 
−
|2009-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#CPX-351_monotherapy_3|CPX-351]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS12
 
−
|-
 
−
|}
 
−
''Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
 
−
'''28-day cycle for 1 to 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. [https://doi.org/10.1200/jco.1991.9.7.1210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2045861 PubMed]
 
−
#'''ECOG E2995:''' Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004  Jul 1;22(13):2747. [https://doi.org/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020609 PubMed]
 
−
#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. [https://doi.org/10.1200/jco.2005.09.133 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1002/cncr.28974 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25223583 PubMed] NCT00822094
 
−
#'''D18-11141:''' NCT03926624
 
−
=Consolidation after salvage therapy=
 
−
==BuCy, then allo HSCT {{#subobject:83e07a|Regimen=1}}==
 
−
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 12.8/120 {{#subobject:eeaff3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00200-4 Rambaldi et al. 2015 (GITMO-AMLR2)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#BuFlu.2C_then_allo_HSCT|BuFlu, then allo HSCT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior 1-year non-relapse mortality
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ Scott et al. 2017 (BMT CTN 0901)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|RIC allo HSCT
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|eeaff3}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 16/200 {{#subobject:334af6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198312013092202 Santos et al. 1983]
 
−
|1975-1982
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|334af6}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. [https://doi.org/10.1056/NEJM198312013092202 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6355849 PubMed]
 
−
#'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957
 
−
#'''BMT CTN 0901:''' Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. [https://doi.org/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28380315 PubMed] NCT01339910
 
−
==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}==
 
−
BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine
 
−
<br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:d415a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00200-4 Rambaldi et al. 2015 (GITMO-AMLR2)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#BuCy.2C_then_allo_HSCT|BuCy, then allo HSCT]]
 
−
| style="background-color:#fc8d59" |Seems to improve 1 & 2 year NRM, similar OS
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|d415a}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:d415b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ Andersson et al. 2008]
 
−
|1997-2005
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#fc8d59" |Suggested improved outcomes, but shorter follow up
 
−
|}
 
−
{{#lst:Allogeneic HSCT|d415b}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:d415c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.40.2362 Lee et al. 2012 (COSAH C-005)]
 
−
|2005-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#BuCy.2C_then_allo_HSCT|BuCy, then allo HSCT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|d415c}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [http://www.bbmt.org/article/S1083-8791(08)00118-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18489993 Pubmed]
 
−
#'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23129746 PubMed] NCT00774280
 
−
#'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957
 
−
==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a408ed|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2015.226 Middeke et al. 2015 (BRIDGE)]
 
−
|2012-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Limited details are available in the abstract. Treatment is meant to be given during aplasia.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]] salvage
 
−
{{#lst:Allogeneic HSCT|a408ed}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed]
 
−
=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 {{#subobject:531b70|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:39f96a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/116/19/3735.long Thepot et al. 2010]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.52.8562 Roboz et al. 2014 (CLAVELA)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Elacytarabine_monotherapy_77|Elacytarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: CLAVELA does not contain precise dosing information for the control arm regimens.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
 
−
'''28-day cycle for at least 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
#Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. [http://www.bloodjournal.org/content/116/19/3735.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20664061 PubMed]
 
−
#'''CLAVELA:''' Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. [https://doi.org/10.1200/jco.2013.52.8562 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24841975/ PubMed] NCT01147939
 
−
==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:596d8b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ Eghtedar et al. 2012 (MDACC 2007-0925)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day
 
−
**Patients with progression were allowed to increase the dose to 50 mg PO twice per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- This study was presented in part at the American Society of Hematology annual meeting, December 2010, Orlando, FL. -->
 
−
#'''MDACC 2007-0925:''' Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. [http://www.bloodjournal.org/content/119/20/4614.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22422826 PubMed]
 
−
=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. [https://doi.org/10.1200/jco.1990.8.5.813 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2185339 PubMed]
 
−
==Revised International Working Group recommendations (2003)==
 
−
#Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. [https://doi.org/10.1200/jco.2003.04.036 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14673054 PubMed]
 
−
=Prognosis=
 
−
==Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)==
 
−
*Relapse-free interval from first complete remission
 
−
**Greater than 18 months (0 points)
 
−
**7 to 18 months ('''3 points''')
 
−
**Less than or equal to 6 months ('''5 points''')
 
−
*Cytogenetics at diagnosis
 
−
**t(16;16) or inv(16) with or without additional cytogenetic abnormalities (0 points)
 
−
**t(8;21) with or without additional cytogenetic abnormalities ('''3 points''')
 
−
**Normal, intermediate, unfavorable, or unknown cytogenetics ('''5 points''')
 
−
*Age at time of first relapse
 
−
**Less than or equal to 35 years (0 points)
 
−
**36 to 45 years ('''1 point''')
 
−
**Greater than 45 years ('''2 points''')
 
−
*Stem cell transplantation performed before first relapse
 
−
**No (0 points)
 
−
**Yes, autologous or allogeneic ('''2 points''')
 
−
Risk stratification:
 
−
*'''1 to 6 points''': Favorable risk (1-year OS of 70%; 5-year OS of 46%)
 
−
*'''7 to 9 points''': Intermediate risk (1-year OS of 49%; 5-year OS of 18%)
 
−
*'''10 to 14 points''': Poor risk (1-year OS of 16%; 5-year OS of 4%)
 
−
</div></div>
 
−
===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. [https://doi.org/10.1200/jco.2005.06.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15632409 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. [https://doi.org/10.1056/NEJMoa074306 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18450602 PubMed]
 
−
#''CEBPA double mutations:'' Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. [https://ashpublications.org/blood/article/113/13/3088/24746/Double-CEBPA-mutations-but-not-single-CEBPA link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19171880 PubMed]
 
−
==Whole genome sequencing==
 
−
#''Seminal paper comparing WGS to cytogenetic analysis:'' Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. [https://doi.org/10.1056/nejmoa2024534 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33704937/ PubMed]
 
−
=Investigational agents=
 
−
''These are drugs under study with at least some promising results for this disease.''
 
−
*[[Alvocidib (Flavopiridol)]]
 
−
*[[Pracinostat (SB939)]]
 
−
*[[Vadastuximab talirine (SGN-CD33A)]]
 
−
*[[Volasertib (BI 6727)]]
 
−
*[[Vosaroxin (SNS 595)]]
 
−
=Additional information=
 
−
[[Category:Acute myeloid leukemia regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Acute leukemias]]
 

Latest revision as of 00:13, 18 June 2023

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