FR901228 in Treating Patients With Hematologic Cancer

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.

Eligibility Criteria:
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