FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT00066638
• Recruitment Status: Completed
• First Posted: August 7, 2003
• Last Update Posted: March 17, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

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

Condition or disease	Intervention/treatment	Phase
DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma	Drug: Romidepsin; Other: Laboratory Biomarker Analysis	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Depsipeptide in Relapsed/Refractory Multiple Myeloma
• Study Start Date: June 2003
• Actual Primary Completion Date: May 2007
• Actual Study Completion Date: March 2011

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures :

1. Response rate (complete response [CR] or partial response [PR]) [ Time Frame: Up to 8 years ]
2. Event free survival [ Time Frame: Up to 8 years ]

Secondary Outcome Measures :

1. Gene array parameters [ Time Frame: Up to 8 years ]
   This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.
2. Immunochemistry parameters [ Time Frame: Up to 8 years ]
   This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467-2490

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ruben Niesvizky-Iszaevich; Montefiore Medical Center - Moses Campus

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00066638
• Other Study ID Numbers: NCI-2012-03005; NCI-2012-03005 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); NCI-5996; 0403-765 ( Other Identifier: Montefiore Medical Center - Moses Campus ); 5996 ( Other Identifier: CTEP ); N01CM62204 ( U.S. NIH Grant/Contract ); P30CA013330 ( U.S. NIH Grant/Contract )
• First Posted: August 7, 2003
• Last Update Posted: March 17, 2015
• Last Verified: December 2012

Additional relevant MeSH terms:

Multiple Myeloma; Romidepsin; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Antibiotics, Antineoplastic; Antineoplastic Agents