Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

Inclusion Criteria:

• Acute myeloid leukemia (AML) as defined by WHO criteria, any subtype, de novo or secondary, except acute promyelocytic leukemia (APL)

• One of the following:

  • Previously untreated, with adverse-risk cytogenetics, including any one of the following:

    • Complete or partial deletion of chromosome 7
    • Complete or partial deletion of chromosome 5
    • At least 3 numerical or structural abnormalities, other than t(15;17), t(8;21) or inv(16) or variant
    • 11q23 abnormalities
    • Inv(3) or variant such as t(3;3)
  • Previously untreated, transformed from prior myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) other than CML
  • Persistent leukemia following one cycle of 3+7 induction therapy (cytarabine plus either daunorubicin or idarubicin), any cytogenetic risk group
• Left ventricular ejection fraction (LVEF) > 50% based on MUGA scan or 2-D echocardiogram
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5x ULN
• Serum AST or ALT ≤ 2.5 x ULN
• ECOG performance status 0-2 (Karnofsky ≥ 60%)

• WBC ≤ 100 x 10^9/L

  • Hydroxyurea to reduce the WBC is permitted up to 24 hours prior to starting chemotherapy
• Fertile patients must use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document
• No patients who have had chemotherapy, radiotherapy, or investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• No patients who have received prior radiation greater than 3000 cGy to marrow-producing areas
• Patients may not be receiving any other investigational agents

• No patients with active CNS leukemia

  • Prior CNS leukemia is permitted provided the cerebrospinal fluid has cleared and there is no other evidence of active CNS leukemia
• No prior therapy for AML with decitabine, azacitidine, mitoxantrone, or etoposide
• No prior therapy with azacitidine or decitabine for pre-existing MDS
• No history of allergic reactions attributed to decitabine, azacitidine, etoposide, mitoxantrone, or compounds of similar chemical or biologic composition

• No uncontrolled intercurrent illness including, but not limited to:

  • Active uncontrolled infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirement
• HIV-positive patients with CD counts less than 500/mm^3 and/or a history of HIV/AIDS-related complications will be excluded from the study