Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI AECM-0403765 NCI-5996, NCT00066638, 5996

Objectives

1. Determine the safety and efficacy of FR901228 (depsipeptide) in patients with relapsed or refractory multiple myeloma.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed multiple myeloma
  • Stage IIa or IIIa
  • Progressive disease after 1-4 prior lines of therapy



• Measurable disease, defined by 1 of the following:
  • Serum M protein at least 1.0 g/dL by protein electrophoresis or free light chain measurement
  • Quantitative immunoglobulins and/or urinary M protein excretion at least 200 mg/24 hours



• No known neoplastic CNS abnormality



• No non-secretory disease or plasma cell leukemia (circulating plasma cells greater than 2,000/mm³)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior histone deacetylase inhibitors

Endocrine therapy

• No concurrent initiation of corticosteroid therapy for myeloma

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent localized external beam radiotherapy

Surgery

• No concurrent surgery

Other

• No other concurrent investigational agent
• No concurrent hydrochlorothiazides

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%
  • Karnofsky 60% allowed if reduced status is due to advanced skeletal disease

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count (ANC) at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Cytopenias due to myeloma marrow infiltration are allowed provided all of the following are true:
  • Bone marrow biopsy displays at least normal cellularity for age and at least 50% involvement by myeloma
  • ANC greater than 1,000/mm³
  • Platelet count greater than 50,000/mm³

Hepatic

• Bilirubin less than 2.0 mg/dL
• SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• No left ventricular hypertrophy
• No cardiac arrhythmias, including atrial fibrillation
• No myocardial infarction
• No symptomatic congestive heart failure
• No unstable angina pectoris
• Ejection fraction at least 50%
• EKG normal

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No known inflammatory, vascular, or degenerative CNS abnormality
• No epilepsy
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to FR901228
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent illness that would preclude study compliance

Expected Enrollment

A total of 21-50 patients will be accrued for this study within 5-12.5 months.

Outcomes

Response rate (complete and partial)

Event-free survival
Response duration
Median time to progression
Rate and duration of stable disease
Gene array and immunochemistry parameters
Comparison of patterns of gene and phenotype expression at baseline and after completion of study treatment

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.

Trial Contact Information

Trial Lead Organizations

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Ruben Niesvizky, MD, Principal investigator		Ph: 212-746-3964

Registry Information
Official Title		A Phase II Study Of Depsipeptide (NSC 630176; IND #51, 810) In Relapsed/Refractory Multiple Myeloma
Trial Start Date		2003-10-02
Registered in ClinicalTrials.gov		NCT00066638
Date Submitted to PDQ		2003-06-27
Information Last Verified		2006-04-20
NCI Grant/Contract Number		CM17103