VNP40101M Followed by Cytarabine in Treating Older Patients With Acute Myeloid Leukemia

DISEASE CHARACTERISTICS:

• Histologically confirmed de novo acute myeloid leukemia (AML)

  • No acute promyelocytic leukemia [t(15;17)]
  • No favorable cytogenetics, including t(15;17), t(8;21), or inv 16
  • No secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS] or myeloproliferative disease), or history of prior chemotherapy or radiation for a disease other than AML

• Must have ≥ 1 of the following poor-risk features:

  • Any of the following unfavorable cytogenetics:

    • Del (5q)/-5q
    • -7/del(7q)
    • Abnormal 3q, 9q, 11q, 20q, 21q, or 17p
    • t(6;9)
    • t(9;22)
    • Trisomy 8
    • Complex karyotypes (≥ 3 unrelated abnormalities)
  • At least 70 years of age
  • ECOG performance status (PS) of 2

  • Cardiac dysfunction* that would limit the use of anthracycline therapy, as defined by any of the following:

    • Ejection fraction ≤ 50%
    • History of significant coronary artery disease, defined as ≥ 1 vessel stenosis requiring medical treatment, stent placement, or surgical bypass graft
    • History of congestive heart failure or myocardial infarction

    • Significant arrhythmia, including any of the following:

      • Atrial flutter (excluding atrial fibrillation)
      • Sick sinus syndrome
      • Ventricular arrhythmia

    • Heart valve disease

      • Mitral valve prolapse allowed
    • Other heart disease, at the discretion of the principal investigator

  • Pulmonary dysfunction not related to AML, defined by 1 of the following:

    • DLCO and/or FEV_1 \< 80% and ≥ 50% normal range
    • Dyspnea on slight activity or at rest
    • Requires oxygen
  • Hepatic dysfunction related to chronic hepatitis or liver cirrhosis
  • Other organ dysfunction or comorbidity that precludes standard cytotoxic induction treatment (e.g., "3+7"), at the discretion of the principal investigator NOTE: *Patients with a history of heart disease as defined above must be on appropriate medication and have their disease under control
• No known CNS disease

PATIENT CHARACTERISTICS:

• ECOG PS 0-2
• AST and ALT ≤ 5 times upper limit of normal
• Bilirubin ≤ 2.0 mg/dL
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• No active, uncontrolled infection

  • Patients with an infection who are under active treatment with antibiotics and whose infections are controlled are eligible
  • Chronic hepatitis allowed
• No clinical evidence of ongoing second malignancy unrelated to AML or MDS
• No evidence of left bundle branch block on screening ECG
• No obligate use of cardiac pacemaker or atrial fibrillation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 24 hours since prior metronidazole
• No prior low-dose, single-agent, cytotoxic chemotherapy (e.g., cytarabine, decitabine, or azacitidine)
• No concurrent disulfiram

• No other concurrent standard or investigational therapy for AML except for the following:

  • Concurrent hydroxyurea to control rising white blood cell counts

    • Dosage must be 4-6 grams daily for up to 4 days

  • Concurrent leukapheresis to control blast cell counts

    • Must be completed within the first 5 days of study therapy
    • No more than 2 procedures per day or 4 procedures total
  • Investigational supportive care agents (e.g., antimicrobials or antifungal agents), at the discretion of the protocol sponsor