Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

Summary

The purpose of this study is to compare the effectiveness of two multi-agent chemotherapy regimens using different dosages of cytarabine to eliminate all detectable leukemia.

Timeline

Start

2002-08

Primary completion

2008-07

Completion

2012-06

Outcome

Missed primary endpoint

paper The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 (34%vs 42%, p=0.17). PMID 20451454 ↗

registry Arm 1: (HDAC) vs Arm 2:(LDAC); p = .1559; Odds Ratio (OR) 1.624 (95% CI .832 to 3.205) NCT00136084 ↗

Publications

• Elsayed AH, Rafiee R, Cao X, Raimondi S, Downing JR, Ribeiro R, Fan Y, Gruber TA, Baker S, Klco J, Rubnitz JE, Pounds S, Lamba JK. A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia. Leukemia. 2020 Mar;34(3):735-745. doi: 10.1038/s41375-019-0604-8. Epub 2019 Oct 23.
• Gamazon ER, Lamba JK, Pounds S, Stark AL, Wheeler HE, Cao X, Im HK, Mitra AK, Rubnitz JE, Ribeiro RC, Raimondi S, Campana D, Crews KR, Wong SS, Welsh M, Hulur I, Gorsic L, Hartford CM, Zhang W, Cox NJ, Dolan ME. Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients. Blood. 2013 May 23;121(21):4366-76. doi: 10.1182/blood-2012-10-464149. Epub 2013 Mar 28.
• Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010 Jun;11(6):543-52. doi: 10.1016/S1470-2045(10)70090-5. Epub 2010 May 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cytarabine	Small molecule	100 mg/m2	Intravenous
Subject	Cytarabine	Small molecule	500 mg/m2	Intravenous
Subject	Cytarabine	Small molecule	1000 mg/m2	Intravenous
Subject	Cytarabine	Small molecule	3000 mg/m2	Intravenous
Subject	Gemtuzumab Ozogamicin	Monoclonal antibody	3 mg/m2	Intravenous
Subject	Gemtuzumab Ozogamicin	Monoclonal antibody	6 mg/m2	Intravenous
Background	Cladribine	Small molecule	9 mg/m2	Intravenous
Background	Cyclophosphamide	Other / unclassified	—	—
Background	Daunorubicin	Small molecule	50 mg/m2	Intravenous
Background	Dexamethasone	Small molecule	—	—
Background	Etoposide	Small molecule	100 mg/m2	Intravenous
Background	Etoposide	Small molecule	125 mg/m2	Intravenous
Background	L-asparaginase	Protein / enzyme biologic	6000 unknown	Intramuscular
Background	MERCAPTOPURINE ANHYDROUS	Small molecule	—	—
Background	Methotrexate	Small molecule	—	—
Background	Mitoxantrone	Small molecule	10 mg/m2	Intravenous
Background	Prednisone	Other / unclassified	—	—
Background	Vincristine	Small molecule	—	—

Indications