FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

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

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

Study Overview

• Status: Completed
• Conditions: Refractory Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Romidepsin

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (romidepsin); 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Romidepsin; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ruben Niesvizky-Iszaevich, Montefiore Medical Center - Moses Campus

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): March 17, 2015
• Last Update Submitted That Met QC Criteria: March 16, 2015
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Antibiotics, Antineoplastic; Romidepsin
• Other Study ID Numbers: NCI-2012-03005 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA013330 (U.S. NIH Grant/Contract); N01CM62204 (U.S. NIH Grant/Contract); 5996 (Other Identifier: CTEP); NCI-5996; 0403-765 (Other Identifier: Montefiore Medical Center - Moses Campus)