VNP40101M in Treating Patients With Acute Myelogenous Leukemia or High-Risk Myelodysplasia

OBJECTIVES:

• Determine the complete response rate to VNP40101M in patients with acute myelogenous leukemia or high-risk myelodysplasia .
• Determine the toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified to acute myelogenous leukemia (AML) or high risk myelodysplasia (MDS) patients ≥ 60 years old with no prior treatment vs AML patients any age in first relapse. (AML patients any age in first relapse closed to accrual 06/09/05).

Patients receive VNP40101M IV over 30 minutes once on day 1 (course 1).

Four to five weeks after the first course, patients undergo bone marrow aspiration and biopsy. If the bone marrow is improved but contains residual leukemia, patients receive a second course of VNP40101M (at the same dose as in course 1). If patients achieve complete response (CR), or partial CR after the first or second course, a consolidation course may be given comprising VNP40101M at a reduced dose.

Patients are followed monthly for 6 months, every 2 months for 12 months, and then every 3 months for 18 months .

PROJECTED ACCRUAL: A total of 230 patients (100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 130 with AML in first relapse) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Acute myelogenous leukemia (AML), meeting the following criteria:

• In first relapse after first treatment-induced complete remission (CR) (closed to accrual as of 06/09/05)

• Duration of first CR less than 12 months
• No prior treatment for first relapse except hydroxyurea
• FAB type M0, M1, M2, M4-7
• No acute promyelocytic leukemia
• No prior treatment with a standard induction regimen containing cytotoxic agents* (for patients 60 years of age or older)
• High-risk myelodysplasia, meeting the following criteria:

• 60 years of age and over
• No prior cytotoxic chemotherapy* except hydroxyurea
• Prior gemtuzumab ozogamicin allowed
• High risk defined as International Prognostic Scoring System score ≥ 1.5, defined by cytogenetics, % marrow blasts, and lineage cytopenias NOTE: *Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• ALT or AST ≤ 5 times upper limit of normal
• Chronic hepatitis allowed

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No myocardial infarction within the past 3 months
• No symptomatic coronary artery disease
• No uncontrolled arrhythmias
• No uncontrolled congestive heart failure
• No other active heart disease

Other

• No uncontrolled active infection
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Up to 4 leukapheresis procedures allowed during the first 15 days of study treatment

Chemotherapy

• See Disease Characteristics
• Concurrent additional hydroxyurea (maximum dose of 5 g daily for up to 4 days) allowed between days 4 and 15 of each study course to control elevated blast levels

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Recovered from all prior therapy
• At least 72 hours since prior anti-leukemic treatment with a non-cytotoxic agent
• No concurrent disulfiram (Antabuse)
• No other concurrent anticancer drugs except anagrelide within the first 15 days of study treatment to control elevated platelet counts
• No other concurrent treatment for leukemia, except hydroxyurea used during study treatment
• No other concurrent investigational drugs