Holkova, Beata, Kmieciak, Maciej, Bose, Prithviraj, Yazbeck, Victor Y., Barr, Paul M., Tombes, Mary Beth, Shrader, Ellen, Weir-Wiggins, Caryn, Rollins, April D., Cebula, Erin M., Pierce, Emily, Herr, Megan, Sankala, Heidi, Hogan, Kevin T., Wan, Wen, Feng, Changyong, Peterson, Derick R., Fisher, Richard I., Grant, Steven, and Friedberg, Jonathan W.
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. [ABSTRACT FROM AUTHOR]