Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Carfilzomib (PR-171) in Combination With Vorinostat (SAHA) in Patients With Relapsed/Refractory B-Cell Lymphomas|
- Number of Participants who experience Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From date of study entry until the 30 days after the last dose of study treatment. ]Determine the recommended phase II doses for the combination of carfilzomib and vorinostat in patients with relapsed or refractory B cell lymphoma.
- Number of Participants who Respond to Treatment [ Time Frame: From the date of completion of first cycle of treatment until the date of best response to treatment, as determined by restaging scans ]Determine response rate to combination of carfilzomib and vorinostat.
|Study Start Date:||January 2011|
|Study Completion Date:||January 2015|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
|Experimental: Vorinostat + Carfilzomib||
Drug: Drug: Carfilzomib
Carfilzomib 30 minutes infusion daily for days 1, 2, 8, 9, 15, 16, Every 28 days. A maximum of 13 cycles will be administered.
Other Name: PR-171Drug: Vorinostat
Vorinostat by mouth twice daily on days 1, 2, 3, 8, 9, 10, 15, 16 and 17. Maximum 13 cycles.
Other Name: Zolinza®
Vorinostat, a class I/II pan-histone deacetylase inhibitor (HDACI), was the first approved agent og this class on the basis of activity in refractory cutaneous T-cell Lymphoma. Lethal mechanisms include anti-apoptotic protein down-regulation, up-regulation of proapoptotic proteins, induction of ROS, death receptor up-regulation, and disruption of chaperone function and DNA-repair proteins.
Carfilzomib, is a irreversible proteasome inhibitor of the epoxyketone class that exhibits a high level of selectivity for the proteosome. This agent induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis.
Study Drug Administration:
If you are found to be eligible to take part in this study:
- Vorinostat PO twice daily on Days 1, 2, 3, 8, 9, 10, 15, 16 and 17.
- Daily Carfilzomib 30 minutes infusion on Days 1, 2, 8, 9, 15, 16.
- Administer first daily dose of vorinostat prior to carfilzomib on Days 1, 2, 8, 9, 15, 16
- Cycle repeated every 28 days, up to 13 cycles.
Carfilzomib will be given at 20mg/m2 for days 1 and 2 of cycle 1 only, then escalated to the higher dose indicated in the schema on day 8 of cycle 1 and thereafter. Carfilzomib treatment is to be done early in the morning and have a minimum of a 6 hour observation period after the infusion. For patients with good tolerability to carfilzomib during the first cycle, an observation period of 2 hours is recommended. A minimum of 16 hours should separate doses of carfilzomib, so that the day 1 dose may be given in the afternoon and the day 2 dose in morning during cycle 2 and subsequent cycles for patients who tolerate the drug well.
If two out of 6 patients do not tolerate the initial dose of 20 mg/m2 carfilzomib on days 1 & 2 followed by 27 mg/m2 carfilzomib for subsequent doses and 200 mg/day bid vorinostat, the next patient should be dose reduced to 20 mg/m2 carfilzomib and 100 mg/day bid vorinostat.
- Baseline within 4 weeks of Cycle 1 Day 1.
- CT or physical exam.
- Bone marrow if needed to follow disease status.
- PET recommended but not required. To document complete response (CR), a PET is REQUIRED.
- Optional research tumor biopsy.
- Peripheral blood obtained for PD prior to initiation of treatment and at 48 hours +/- 6 hours after receiving first dose of Carfilzomib , and at Off Study.
- End of Treatment Restaging will take place 6-8 weeks after completion of treatment and will include an assessment by the physician, labs, and a tumor response evaluation.
- After completion of Restaging exams, Follow up exams will take place every 6 months for 2 years and then annually until disease progression or initiation of another treatment.
- An Off Study visit will take place at the time of disease progression or initiation of another treatment, which will include assessment by the physician,a tumor response evaluation, labs, and a final PD sample, by the patient's consent.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01276717
|United States, New York|
|University of Rochester|
|Rochester, New York, United States, 14642|
|United States, Virginia|
|Virginia Commonwealth University Massey Cancer Center|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Jonathan Friedberg, M.D.||University of Rochester|