RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of FR901228 in treating patients who have hematologic cancer.

OBJECTIVES:

• Determine the in vivo biologic effect of FR901228 (depsipeptide) in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, acute myeloid leukemia, or acute lymphoblastic leukemia.
• Determine the pharmacokinetics and cellular pharmacodynamics of this drug in these patients.
• Determine any preliminary anti-tumor activity of this drug in these patients.

OUTLINE: This is a dose-decreasing, multicenter study. Patients are stratified according to disease (chronic lymphocytic leukemia and small lymphocytic lymphoma vs acute myeloid leukemia and acute lymphoblastic leukemia).

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 10 patients per stratum receive decreasing doses of FR901228 until the minimal active dose is determined. If 5 or more patients show clinical or biological response, the subsequent cohort is treated at a lower dose. If fewer than 5 patients respond, the subsequent cohort is treated at a higher dose.

PROJECTED ACCRUAL: A minimum of 20 patients (10 per stratum) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following hematologic malignancies:

  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL) (including Waldenstrom's macroglobulinemia)
  • Acute myeloid leukemia (AML)
  • Acute lymphoblastic leukemia (ALL)

• Stratum I (CLL and SLL):

  • Received at least one prior therapy containing a purine analog OR
  • Received another form of therapy (including alkylating agents) due to history of severe autoimmune disease, requirement for chronic corticosteroid, or other contraindication to purine analog therapy

• Stratum II (AML and ALL):

  • Primary refractory or relapsed leukemia within the past year that is not amenable to curative therapy

  • OR

  • Untreated or previously treated poor-risk leukemia defined by any of the following:

    • 65 years of age and over
    • Poor-risk candidates for aggressive chemotherapy
    • Poor-risk cytogenetics (for AML, karyotype abnormalities other than t(8;21), inv(16), t(15;17))

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Stratum I only:

  • No uncontrolled autoimmune hemolytic anemia
  • No idiopathic thrombocytopenic purpura

• Stratum II only:

  • WBC no greater than 10,000/mm^3 OR
  • WBC no greater than 40,000/mm^3 that is stable for at least 1 week (may be sustained by hydroxyurea through the first week of study)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT and AST no greater than 3 times upper limit of normal

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

• Ejection fraction at least 50% by MUGA
• No myocardial infarction or unstable angina within the past 6 months
• No prior unstable ventricular or supraventricular cardiac arrhythmias

Other:

• HIV negative

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other medical or psychiatric problem that would preclude study

• Stratum I only:

  • No active infection requiring oral or IV antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 28 days since prior chemotherapy (except hydroxyurea)
• At least 6 weeks since prior nitrosoureas
• At least 8 weeks since prior UCN-01 (unless plasma UCN-01 level less than 1 uM)

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• At least 28 days since prior radiotherapy

Surgery:

• At least 28 days since prior major surgery