NCT00007345

Depsipeptide to Treat Patients With Cutaneous T-Cell Lymphoma and Peripheral T-Cell Lymphoma

Phase II Trial of Depsipeptide in Patients With Cutaneous T-Cell Lymphoma and Relapsed Peripheral T-Cell Lymphoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 131 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Cutaneous T Cell Lymphoma
• Peripheral T Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Romidepsin

Timeline

• Start date: 2001-03-08
• Primary completion: 2015-01-26
• Completion: 2015-07-27
• First posted: 2000-12-18
• Last updated: 2017-05-16
• Results posted: 2016-02-12

Locations

13 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study