RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug.

PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.

OBJECTIVES:

• Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes.
• Determine the toxic effects of this regimen in these patients.
• Determine the maximum tolerated dose of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups.

• Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.

Cohorts of 3-6 patients receive escalating doses of fludarabine 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, 10 additional patients are treated at that dose level.

• Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours on day 1. Beginning within 4 hours after completion of 3-AP, patients receive fludarabine IV over 30 minutes on days 2-6.

In both groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Drug: fludarabine phosphate
• Drug: triapine

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

  • High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia

    • International Prognostic Scoring System (IPSS) score at least 1.5 based on the following:

      • More than 10% marrow blasts
      • Cytopenias in at least 2 lineages
      • Adverse cytogenetics

  • Acute myeloid leukemia (AML)

    • All subtypes, including MDS/AML and treatment-related (secondary) AML
  • Acute lymphoblastic leukemia

  • Acute progranulocytic leukemia

    • Ineligible for arsenic therapy

  • Chronic myelogenous leukemia

    • Accelerated phase or blastic crisis
  • Chronic lymphocytic leukemia
  • Prolymphocytic leukemia
• Received or ineligible for established curative regimens, including stem cell transplantation
• Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• No history of hemolytic anemia grade 2 or greater

• No known glucose-6-phosphate dehydrogenase (G6PD) deficiency

  • G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)

Hepatic

• SGOT and SGPT no greater than 2.5 times normal
• Bilirubin no greater than 2 mg/dL
• No chronic hepatitis

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

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

Pulmonary

• No dyspnea at rest or with minimal exertion
• No severe pulmonary disease requiring supplemental oxygen

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No neuropathy grade 2 or greater

• No active uncontrolled infection

  • Infections under active treatment and controlled by antibiotics are allowed
• No other life-threatening illness
• No psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, and interleukin-11)
• No concurrent immunotherapy

Chemotherapy

• Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects)
• At least 72 hours since prior hydroxyurea
• At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas)
• No more than 12 prior courses of fludarabine
• No more than 3 prior cytotoxic chemotherapy regimens
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

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

Surgery

• Not specified

Other

• At least 1 week since prior non-myelosuppressive treatment
• No more than 4 prior induction regimens
• No other concurrent therapy