Depsipeptide to Treat Patients With Cutaneous T-Cell Lymphoma and Peripheral T-Cell Lymphoma
Status:
Completed
Trial end date:
2015-07-27
Target enrollment:
Participant gender:
Summary
Background:
NSC630176 is a depsipeptide fermentation product from Chromobacterium violaceum with potent
cytotoxic activity against human tumor cell lines and in vivo efficacy against both human
tumor xenografts and murine tumors (1-3).
NSC 630176, herein referred to as depsipeptide, shows a lack of cross resistance with several
commonly used cytotoxic agents such as vincristine, 5-fluorouracil, mitomycin C and
cyclophosphamide (2). However, it has been defined as a P-glycoprotein (Pgp) substrate by
COMPARE analysis of the National Cancer Institute (NCI) drug screen cytotoxicity profile (4).
Depsipeptide is a member of a novel class of antineoplastic agents, the histone deacetylase
inhibitors.
In the phase I trial conducted at the National Cancer Institute (NCI), responses were
observed at the maximum tolerated dose (MTD) in patients with cutaneous and peripheral T-cell
lymphoma.
Objectives:
In patients with cutaneous T-cell lymphoma, the primary end points to be examined are overall
response rate, complete response rate and duration of response.
In patients with relapsed peripheral T-cell lymphoma, the endpoints to be examined are
overall response rate and complete response rate.
To evaluate the tolerability of depsipeptide with extended cycles of therapy.
Eligibility:
Patients with cutaneous T-cell lymphoma (mycosis fungoides or Sezary syndrome) or other
peripheral T-cell lymphomas are eligible.
Design:
Depsipeptide will be administered at 14 mg/m^2, over 4 hours on days 1, 8 and 15.
This trial will accrue in six cohorts; Arm 1, patients with cutaneous T-cell lymphoma who
have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 2, patients
with peripheral T-cell lymphoma who have had less than or equal to two prior cytotoxic
chemotherapy regimens; Arm 3, patients with cutaneous and peripheral T-cell lymphoma who have
had more than two prior cytotoxic chemotherapy regimens; Arm 4, patients with other mature
T-cell lymphomas; Arm 5, a replicate arm of arm 1; Arm 6, patients with peripheral T-cell
lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 7, patients
with cutaneous T cell lymphoma who have received vorinostat.
Dose may be adjusted based on toxicities.