Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma
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|ClinicalTrials.gov Identifier: NCT01276717|
Recruitment Status : Completed
First Posted : January 13, 2011
Last Update Posted : December 3, 2015
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: Drug: Carfilzomib Drug: Vorinostat||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of Carfilzomib (PR-171) in Combination With Vorinostat (SAHA) in Patients With Relapsed/Refractory B-Cell Lymphomas|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||January 2015|
|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®
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|