FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Phase 2

Terminated

Conditions: Recurrent Mantle Cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma

Interventions: Drug: romidepsin

Registration Number: NCT00383565

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Detailed Description: OBJECTIVES:

I. Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma.

II. Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients.

III. Determine 2-year progression-free and overall survival.

OUTLINE: Patients receive FR901228 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.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:
- Mantle cell lymphoma
- Diffuse large cell lymphoma
- (Ineligible for or unwilling to undergo stem cell transplantation)
Relapsed or refractory disease:
- Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation
- No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease
Measurable disease, defined as >= 1 lesion >= 1.5 cm in the longest diameter
No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma)
ECOG performance status 0-2
Absolute neutrophil count >= 1,000/mm^3 OR >= 500/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
Platelet count >= 75,000/mm^3 OR >= 50,000/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
Bilirubin normal
Alkaline phosphatase =< 2 times upper limit of normal (ULN)
AST =< 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure
No history of serious ventricular arrhythmia
QTc < 500 msec
No evidence of cardiac hypertrophy on ECG
No known HIV positivity
No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes)
Recovered from prior therapy
No prior doxorubicin hydrochloride >= 450 mg/m^2 or mitoxantrone >= 112 mg/m^2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" < 450 mg/m^2
No prior therapy with a histone deacetylase inhibitor
No concurrent dexamethasone or prednisone except for refractory nausea/vomiting
No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate)
Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic)
No CNS lymphoma
Creatinine normal
Cardiac function >= 50% by MUGA

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	romidepsin	Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.

Primary Outcome Measures

Name	Time	Method
Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment	24 weeks (6 courses of 4 week cycles)	International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen.

Secondary Outcome Measures

Name	Time	Method
Median Progression Free-survival (PFS)	2 Years	Time to disease progression is defined as the time from registration to documentation of disease progression.
Median Overall Survival	5 Years	Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier.