FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066638
First received: August 6, 2003
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: romidepsin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Depsipeptide in Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete response [CR] or partial response [PR]) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Event free survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Gene array parameters [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.

  • Immunochemistry parameters [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    This analysis will be descriptive and will compare patterns of gene and phenotype expression pre and post therapy.


Enrollment: 50
Study Start Date: June 2003
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Names:
  • FK228
  • FR901228
  • Istodax
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066638

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Ruben Niesvizky-Iszaevich Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00066638     History of Changes
Other Study ID Numbers: NCI-2012-03005, NCI-2012-03005, NCI-5996, 0403-765, 5996, N01CM62204
Study First Received: August 6, 2003
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
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
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014