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 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.
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.