OBJECTIVES:

Primary

• Determine the maximum tolerated dose of 3-AP (Triapine®) administered with high-dose cytarabine in patients with advanced hematologic malignancies.

Secondary

• Determine the clinical activity of this regimen in these patients.
• Determine the effect of treatment with 3-AP (Triapine®) on intracellular levels of cytarabine in these patients.

OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).

Patients receive high-dose cytarabine IV over 2 hours on days 1-5 and 3-AP (Triapine®) IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in each stratum receive escalating doses of 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for up to 2 years.

PROJECTED ACCRUAL: A total of 6-48 patients (3-24 per stratum) will be accrued for this study within 15-24 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following hematologic malignancies:

  • Relapsed or refractory acute myeloid leukemia (AML)
  • Relapsed or refractory acute lymphoblastic leukemia
  • Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes or myeloproliferative disorders OR therapy-related AML
  • Chronic myeloid leukemia in accelerated or blast phase
• Refractory to standard therapy or no standard therapy exists
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• CALGB 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• No G6PD deficiency

Hepatic

• Bilirubin < 2.0 mg/dL (unless due to Gilbert's syndrome)
• AST and ALT < 2.5 times upper limit of normal (ULN)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No pulmonary disease requiring oxygen

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to study drugs
• No neuropathy
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic agents

Chemotherapy

• At least 72 hours since prior hydroxyurea
• At least 2 weeks since other prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

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

Surgery

• Not specified

Other

• Recovered from all prior therapy
• At least 4 weeks since prior investigational agents
• No other concurrent investigational therapy
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients