A Phase II Study of Depsipeptide, a Histone Deacetylase Inhibitor, in Relapsed or Refractory Mantle Cell or Diffuse Large Cell 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
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.
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.
Inclusion Criteria:
Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:
Relapsed or 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