Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days. Dose escalation initially followed a standard 3 + 3 design, but adapted a more conservative accrual rule following dose de-escalation. The maximum tolerated dose was 20 mg/m2 carfilzomib and 100 mg vorinostat (twice daily). The dose-limiting toxicities were grade 3 pneumonitis, hyponatremia, and febrile neutropenia. One patient had a partial response and two patients had stable disease. Correlative studies showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response.
Authors: Beata Holkova, Maciej Kmieciak, Prithviraj Bose, Victor Y. Yazbeck, Paul M. Barr, Mary Beth Tombes, Ellen Shrader, Caryn Weir-Wiggins, April D. Rollins, Erin M. Cebula, Emily Pierce, Megan Herr, Heidi Sankala, Kevin T. Hogan, Wen Wan, Changyong Feng, Derick R. Peterson, Richard I. Fisher, Steven Grant, Jonathan W. Friedberg
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1671254148