Clinical Trial: Study of Oral Bexarotene in Combination With Photopheresis for Treatment of Cutaneous T-Cell Lymphoma
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Phase I/II Study of Oral Bexarotene in Combination With Photopheresis for Treatment of Cutaneous T-Cell Lymphoma
Brief Summary: This is a pilot study of the safety and tolerability of photopheresis in combination with increasing doses of oral bexarotene in patients with cutaneous T-cell lymphoma.Our hypotheses are that the combination of bexarotene with photopheresis is safe and that bexarotene will enhance immune response in the setting of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma (CTCL), resulting in a shorter time to clinical response.
Detailed Summary:
Photopheresis is FDA-approved as a device in the treatment of patients with cutaneous T-cell lymphoma. Using treatment schedules of once monthly treatment, with each treatment consisting of two consecutive days of photopheresis, initial response rates of 20-60% have been reported. However, in publications, for those who attained a complete response, median time to response was 11 months (range 5 to 14 months). Response has been shown to correlate with intact immune function in patients with normal CD8+ cell prior to therapy. The mechanism of activity of photopheresis in cutaneous T-cell lymphoma while not fully understood involves apoptosis of malignant tumor cells. Modifications in the original scheduling of photopheresis, with shorter cycles of 2 or 3 weeks, have met with success. Several centers have been using an accelerated delivery schedule of treatments, treating patients every 2 weeks.
Bexarotene was FDA approved for patients with CTCL. It is an RXR selective retinoid. Retinoids can serve as physiologic rather than cytotoxic drugs to arrest or reverse the process of carcinogenesis. There is a growing body of evidence that supports a role for retinoids in the induction of apoptosis. In the two, completed Phase II-III studies that formed the basis of approval (approved dose is 300mg/m2/day) of bexarotene capsules, 193 patients with previously treated CTCL were administered bexarotene capsules. Response rates were in the order of 50% for the 300mg/2/day, however, 79% of patients had hyperlipidemia.
This study will therefore primarily examine the safety and tolerability of using increasing doses of bexarotene in combination with photopheresis. As a secondary endpoint, we will attempt to establish whether bexarotene can upregulate the immune response and therefore potentially enhance the response rates to photopheresis
Sponsor: Boston University
Current Primary Outcome: Safety and tolerability of bexarotene in combination with ECP, assessed with NCI toxicity assessment, at each treatment visit, every 3 weeks and at final one month foll
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Time to response of bexarotene with ECP in patients with CTCL, at month 4 (follow-up visit) patient’s response by organ system involvement, with an overall assessment: complete response, partial response, no change, or progressive disease, flare.
- Another secondary outcome is whether combination of instruments provides relevant information on CTCL patients' health related quality of life during therapy
Original Secondary Outcome: Same as current
Information By: Boston University
Dates:
Date Received: March 23, 2006
Date Started: December 2001
Date Completion: April 2004
Last Updated: March 23, 2006
Last Verified: September 2004
