NCT01276717

Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma

Phase I Trial of Carfilzomib (PR-171) in Combination With Vorinostat (SAHA) in Patients With Relapsed/Refractory B-Cell Lymphomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Rochester · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This will be a phase I study of carfilzomib in combination with vorinostat in patients with relapsed/refractory B-cell lymphomas. Combination therapy with proteosome inhibitor PR-171 and HDAC inhibitors is highly synergistic in primary DLBCL cells, and both classes of drugs can also synergize powerfully to induce cell death in bortezomib-resistant cells. The purpose of this study is to see if vorinostat can combine with carfilzomib and to safely find the recommended phase II dose.

Detailed description

Study Drugs: 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. Study Visits: * 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.

Conditions

• Lymphoma

Interventions

Type	Name	Description
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.
DRUG	Vorinostat	Vorinostat by mouth twice daily on days 1, 2, 3, 8, 9, 10, 15, 16 and 17. Maximum 13 cycles.

Timeline

• Start date: 2011-01-01
• Primary completion: 2013-07-01
• Completion: 2015-01-01
• First posted: 2011-01-13
• Last updated: 2015-12-03

Locations

2 sites across 1 country: United States