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FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Romidepsin
Laboratory Biomarker Analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for DS Stage II Plasma Cell Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Montefiore Medical Center - Moses Campus

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (romidepsin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate (complete response [CR] or partial response [PR])
Event free survival

Secondary Outcome Measures

Gene array parameters
This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.
Immunochemistry parameters
This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.

Full Information

First Posted
August 6, 2003
Last Updated
March 16, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00066638
Brief Title
FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase 2 Study of Depsipeptide in Relapsed/Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (romidepsin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Romidepsin
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response rate (complete response [CR] or partial response [PR])
Time Frame
Up to 8 years
Title
Event free survival
Time Frame
Up to 8 years
Secondary Outcome Measure Information:
Title
Gene array parameters
Description
This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.
Time Frame
Up to 8 years
Title
Immunochemistry parameters
Description
This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.
Time Frame
Up to 8 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruben Niesvizky-Iszaevich
Organizational Affiliation
Montefiore Medical Center - Moses Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States

12. IPD Sharing Statement

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FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

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