3-AP and Cytarabine in Treating Patients With Hematologic Cancer

OBJECTIVES:

• Determine the feasibility, tolerability, and toxic effects of 3-AP in combination with cytarabine in patients with hematologic malignancies.
• Determine the maximum tolerated dose and phase II dose of cytarabine in this regimen in these patients.
• Determine the biological effects of 3-AP and its interaction with cytarabine in these patients.

OUTLINE: This is a pilot, dose-escalation study of cytarabine.

Patients receive 3-AP IV over 6 hours followed by cytarabine IV over 18 hours on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response may receive an additional course as consolidation therapy.

Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose.

PROJECTED ACCRUAL: Approximately 20-25 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

• Acute myeloid leukemia
• Acute lymphoblastic leukemia
• Chronic myelogenous leukemia (CML)
• CML in blast crisis
• Chronic lymphocytic leukemia
• High-risk* myelodysplastic syndromes, including the following:

• Refractory anemia with excess blasts (RAEB)
• RAEB in transformation
• Chronic myelomonocytic leukemia NOTE: *High-risk myelodysplasia defined as having an International Performance Scoring System score of at least 1.5, based on adverse cytogenetics, greater than 10% blasts in marrow, and cytopenias in at least 2 lineages
• Relapsed or refractory disease
• Ineligible for higher priority protocols

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 2 months

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 2.0 mg/dL (unless considered due to malignancy)
• ALT or AST no greater than 3 times upper limit of normal
• Chronic hepatitis allowed

Renal

• Creatinine no greater than 2.0 mg/dL (unless considered due to malignancy)

Cardiovascular

• No myocardial infarction within the past 3 months
• No symptomatic coronary artery disease
• No arrhythmias (other than atrial fibrillation or flutter) requiring treatment
• No uncontrolled congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Concurrent infections under active treatment with and controlled by antibiotics allowed
• No other concurrent life-threatening illness
• No mental deficit or psychiatric history that would preclude giving informed consent or complying with protocol

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior growth factors, including the following:

• Epoetin alfa
• Filgrastim (G-CSF)
• Sargramostim (GM-CSF)
• Interleukin-3
• Interleukin-11
• No concurrent anticancer immunotherapy

Chemotherapy

• At least 72 hours since prior hydroxyurea
• Recovered from prior chemotherapy
• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• Not specified

Other

• At least 3 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
• At least 1 week since prior nonmyelosuppressive therapy
• No other concurrent standard or investigational therapy for the malignancy