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

PURPOSE: Phase II trial to study the effectiveness of FR901228 in treating patients who have relapsed or refractory multiple myeloma.

OBJECTIVES:

• Determine the safety and efficacy of FR901228 (depsipeptide) in patients with relapsed or refractory multiple myeloma.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a stable plateau (stable paraprotein levels or urine protein excretion over 3 consecutive determinations at least 4 weeks apart) may receive maintenance therapy comprising FR901228 IV on days 1 and 15, with courses repeating every 28 days.

PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study within 5-12.5 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed multiple myeloma

  • Stage IIa or IIIa
  • Progressive disease after 1-4 prior lines of therapy

• Measurable disease, defined by 1 of the following:

  • Serum M protein at least 1.0 g/dL by protein electrophoresis or free light chain measurement
  • Quantitative immunoglobulins and/or urinary M protein excretion at least 200 mg/24 hours
• No known neoplastic CNS abnormality
• No non-secretory disease or plasma cell leukemia (circulating plasma cells greater than 2,000/mm^3)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

  • Karnofsky 60% allowed if reduced status is due to advanced skeletal disease

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count (ANC) at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

• Cytopenias due to myeloma marrow infiltration are allowed provided all of the following are true:

  • Bone marrow biopsy displays at least normal cellularity for age and at least 50% involvement by myeloma
  • ANC greater than 1,000/mm^3
  • Platelet count greater than 50,000/mm^3

Hepatic

• Bilirubin less than 2.0 mg/dL
• SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No left ventricular hypertrophy
• No cardiac arrhythmias, including atrial fibrillation
• No myocardial infarction
• No symptomatic congestive heart failure
• No unstable angina pectoris
• Ejection fraction at least 50%
• EKG normal

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No known inflammatory, vascular, or degenerative CNS abnormality
• No epilepsy
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to FR901228
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior histone deacetylase inhibitors

Endocrine therapy

• No concurrent initiation of corticosteroid therapy for myeloma

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent localized external beam radiotherapy

Surgery

• No concurrent surgery

Other

• No other concurrent investigational agent
• No concurrent hydrochlorothiazides