FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

PRIMARY OBJECTIVES:

I. To evaluate the safety and efficacy of depsipeptide in patients with refractory or relapsed multiple myeloma (MM).

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.

Inclusion criteria

• Patients must have histologically or cytologically confirmed stage IIa or IIIa multiple myeloma
• Patient has progressive disease and has had 1, 2, 3, or 4 prior lines of therapy
• Bilirubin < 2.0 mg/dL
• SGOT/SGPT =< 2.5 X institutional upper limit of normal
• Serum creatinine =< 1.5 mg/dl OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Karnofsky Performance Status equal or greater than 70%; KPS 60% will be allowed if reduced KPS is due to advanced skeletal disease
• Measurable disease as defined by serum M protein >= 1.0 gm/dl measured by serum protein electrophoresis or free light chain measurement, or quantitative immunoglobulins and/or urinary M protein excretion >= 200 mg/24 hrs
• Ejection fraction >= 50% and normal baseline EKG tracing
• No known central nervous system abnormality including neoplastic, vascular, inflammatory, degenerative or epilepsy
• Life expectancy of greater than 12 weeks
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Patients in whom cytopenias are considered to be due to myeloma marrow infiltration will be allowed as long as they meet the following criteria:

• Bone marrow biopsy displaying >= normal cellularity for age and >= 50% involvement by myeloma
• ANC > 1,000 and platelets > 50,000
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign written informed consent

Exclusion criteria

• Administration of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to enrollment or unresolved adverse events due to agents administered more than 4 weeks earlier
• Prior treatment with a histone deacetylase inhibitor
• Patients may not be receiving any other investigational agent
• History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free >= 5 years)
• Non secretory disease or plasma cell leukemia (> 2000 circulating plasma cells/uL)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to depsipeptide
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with left ventricular hypertrophy or history of arrhythmias including atrial fibrillation, myocardial infarction or congestive heart failure; patients may not be taking hydrochlorothiazides
• Patients that are pregnant or lactating will be excluded from this trial
• Known HIV positivity; patients infected with the HIV virus will be excluded from this trial