| Literature DB >> 26284612 |
Beata Holkova1,2, Maciej Kmieciak1, Prithviraj Bose3, Victor Y Yazbeck1,2, Paul M Barr4, Mary Beth Tombes1, Ellen Shrader1, Caryn Weir-Wiggins1, April D Rollins1, Erin M Cebula4, Emily Pierce4, Megan Herr4, Heidi Sankala1, Kevin T Hogan1, Wen Wan5, Changyong Feng4,6, Derick R Peterson6, Richard I Fisher7, Steven Grant1,2,8,9,10, Jonathan W Friedberg4,11.
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.Entities:
Keywords: Carfilzomib; lymphoma; phase 1 clinical trial; vorinostat
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Year: 2015 PMID： 26284612 PMCID： PMC4798896 DOI： 10.3109/10428194.2015.1075019
Source DB: PubMed Journal: Leuk Lymphoma ISSN： 1026-8022