FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
A Phase II Study Of Depsipeptide, A Histone Deacetylase Inhibitor, In Relapsed Or Refractory Mantle Cell Or Diffuse Large Cell Non-Hodgkin's Lymphoma
Study Overview
Detailed Description
OBJECTIVES:
I. Determine the response rate (complete and partial) in patients with relapsed or refractory Burkitt's, mantle cell or diffuse large cell non-Hodgkin's lymphoma treated with FR901228 (depsipeptide).
II. Determine the safety and feasibility of this drug, in terms of incidence and maximum grade of toxicity and courses delayed or doses reduced, in these patients.
III. Determine the 2-year progression-free survival and overall survival of patients treated with this drug.
IV. Correlate tumor expression of BCL-2, BCL-6, BAX, and RAS with response in patients treated with this drug.
OUTLINE: This is a multicenter study.
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then every 6 months until 5 years from study registration.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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District of Columbia
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Washington, District of Columbia, United States, 20060
- Howard University Cancer Center at Howard University Hospital
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Maryland
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Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Michigan
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Detroit, Michigan, United States, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Wisconsin
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Madison, Wisconsin, United States, 53792-5256
- University of Wisconsin Comprehensive Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following cellular types:
- Diffuse large cell
- Mantle cell
- Burkitt's
Relapsed or refractory disease
- No more than 2 prior regimen for patients with refractory disease
- Any number of prior therapies (including peripheral blood stem cell or bone marrow transplantation) allowed for patients with relapsed disease provided there was an objective response to the most recent therapy
Measurable disease
- At least 1 lesion ≥ 1.5 cm in diameter
- No transformed lymphoma
- No CNS lymphoma
- Ineligible for, refused, or relapsed after stem cell transplantation
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3 (500/mm^3 in patients with extensive bone marrow involvement [> 50%] or hypersplenism with palpable splenomegaly)
- Platelet count ≥ 75,000/mm^3 (50,000/mm^3 in patients with extensive bone marrow involvement or hypersplenism with palpable splenomegaly)
Hepatic
- Bilirubin ≤ upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN
- AST ≤ 2 times ULN
Renal
- Creatinine ≤ ULN
Cardiovascular
- QTc < 500 msec by ECG
- Cardiac function ≥ 50% by MUGA
- No prior serious ventricular arrhythmia
- No New York Heart Association class III or IV congestive heart failure
- No significant cardiac hypertrophy by ECG
- No other significant cardiac disease
Pulmonary
- No chronic obstructive pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No active infection
- No diabetes
- No other uncontrolled serious medical condition
PRIOR CONCURRENT THERAPY:
Chemotherapy
- Prior cumulative doxorubicin dose < 450 mg/m^2
- Prior cumulative mitoxantrone dose < 112 mg/m^2
- Prior doxorubicin equivalent dose < 450 mg/m^2 (for patients who have previously received both doxorubicin and mitoxantrone)
Other
- Recovered from all prior therapy
- No prior histone deacetylase inhibitor therapy
- No concurrent medication associated with QTc prolongation, such as dolasetron
- Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is on concurrent potassium chloride supplementation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm I
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Nancy L. Bartlett, MD, Washington University Siteman Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2012-02571
- MAYO-MC0287
- NCI-5961
- CDR0000349660 (Registry Identifier: PDQ (Physician Data Query))
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