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