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