3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome

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.

Eligibility Criteria:
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