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

Study Overview
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Brief Summary
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This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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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.

Official Title
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A Phase II Study Of Depsipeptide, A Histone Deacetylase Inhibitor, In Relapsed Or Refractory Mantle Cell Or Diffuse Large Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: romidepsin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: romidepsin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma, recurrent mantle cell lymphoma, recurrent adult Burkitt lymphoma