• Response rate (complete and partial) [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Response rate (complete and partial)
• Toxicity

RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory acute myeloid leukemia.

OBJECTIVES:

• Determine the complete and partial response rate in patients with relapsed or refractory acute myeloid leukemia treated with FR901228 (depsipeptide).
• Determine the toxicity of this drug in these patients.
• Correlate clinical response with specific cytogenetic abnormalities in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to the presence of a specific chromosomal abnormality (t[8;21] vs inv 16 vs t[15;17] vs absence of these chromosomal abnormalities).

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 22-47 patients will be accrued for this study within 12-27 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed acute myeloid leukemia (AML) defined by the WHO classification

  • Initial diagnosis with either of the following:

    • Bone marrow or peripheral blood myeloblasts of at least 20%
    • Recurring genetic abnormalities (e.g., t[8;21], inv 16, or t[16;16]) and bone marrow blast percentage less than 20%

• Relapsed or refractory disease defined by 1 of the following:

  • Under 60 years of age and in second relapse or greater

  • Over 60 years of age and in first relapse

    • Patients who are over 60 years of age with previously untreated disease and who refuse conventional chemotherapy are eligible
    • Patients who are over 60 years of age and in first relapse and poor medical candidates for reinduction chemotherapy or who refuse conventional chemotherapy are eligible
  • Acute promyelocytic leukemia that has relapsed despite prior tretinoin and arsenic therapy
  • Primary refractory AML for which no standard therapy exists
• Not medically appropriate for OR refused curative bone marrow or stem cell transplantation
• No CNS leukemia

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST/ALT no greater than 3 times ULN

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• LVEF at least 40% by MUGA
• QTc interval less than 500 msec by EKG
• No myocardial infarction within the past 3 months
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

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 FR901228 (depsipeptide)
• No concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 4 weeks since prior autologous stem cell or bone marrow transplantation
• No prior allogeneic stem cell or bone marrow transplantation
• No concurrent biologic agents

Chemotherapy

• See Disease Characteristics
• At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
• No prior FR901228 (depsipeptide)

• No concurrent chemotherapy

  • Concurrent hydroxyurea allowed during the first course of study therapy to control hyperleukocytosis

Endocrine therapy

• Not specified

Radiotherapy

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

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 4 weeks since prior investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent drugs known to have histone deacetylase inhibitor activity (e.g., sodium valproate)
• No other concurrent antineoplastic agents