Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Inclusion Criteria for Step 1 (Induction):

• Sexually active males must be strongly advised to use an accepted and effective method of contraception
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin = = 70 years of age)
• Patients with secondary AML are eligible for enrollment onto the trial; secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML
• Total serum bilirubin = 1 are eligible if they have a calculated glomerular filtration rate (GFR) of >= 60 ml/min (i.e. class I or class II chronic kidney disease ) using the Modification of Diet in Renal Disease (MDRD) formula
• Note: Daily creatinine and MDRD formula are only for the 1st induction cycle
• Cardiac ejection fraction >= 45% or within institutional normal limits; a nuclear medicine gated blood pool examination is preferred; a two-dimensional (2-D) echocardiogram (ECHO) scan is acceptable if a calculated ejection fraction is obtained and follow-up measurement of the cardiac ejection fraction will also be performed by echocardiography; measurement of cardiac ejection fraction should be within two weeks prior to receiving treatment
• NOTE: when a multi gated acquisition scan (MUGA) or echocardiogram cannot be obtained due to weekend or holiday, then patients may be enrolled provided there is no history of significant cardiovascular disease and a measurement of cardiac ejection fraction will be performed within 5 days of study enrollment
• Patients with suspected central nervous system (CNS) involvement should undergo lumbar puncture
• Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (>10^9/l) from peripheral blood
• HLA typing should be performed at registration, if possible
• Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing

Exclusion Criteria for Step 1 (Induction):

• Concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS])
• Active, uncontrolled infection
• Acute promyelocytic leukemia (APL) confirmed either by the presence of t(15;17)(q22;q21) or promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha transcripts
• Blastic transformation of chronic myelogenous leukemia
• Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine
• Prior chemotherapy for AML with the exception of hydroxyurea for increased blast count or leukapheresis for leukocytosis
• Documented CNS involvement
• Previous treatment for antecedent hematological disorders (AHD) with 5-azacitidine, decitabine, or low dose cytarabine
• Human immunodeficiency virus (HIV) infection

Inclusion Criteria for Step 2 (Consolidation)

• NOTE: All patients achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) will receive consolidation when fit
• NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation treatment
• Consolidation cycle 1 must commence within sixty days of the bone marrow aspirate and biopsy that confirmed the presence of a CR or CRi
• Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant)
• Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
• ECOG performance status of 0-2
• Patients must have resolved any serious infectious complications related to induction
• NOTE: Patients with an HLA-matched donor and proceeding to transplant will be allowed up to one cycle of consolidation treatment
• Any significant medical complications related to induction must have resolved
• Patients must have a creat