FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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Drugs used in chemotherapy such as FR901228 use different ways to stop cancer cells from dividing so they stop growing or die. Phase II trial to study the effectiveness of FR901228 in treating patients who have relapsed or refractory multiple myeloma

Detailed Description
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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.

Official Title
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A Phase 2 Study of Depsipeptide in Relapsed/Refractory Multiple Myeloma

Conditions
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DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma

Intervention / Treatment
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* Drug: Romidepsin
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (romidepsin)<br>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. | Drug: Romidepsin<br>* Given IV<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete response [CR] or partial response [PR]) |  | Up to 8 years | 
| Event free survival |  | Up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene array parameters | This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy. | Up to 8 years | 
| Immunochemistry parameters | This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy. | Up to 8 years |