A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. Issue 6 (3rd June 2017)

• Record Type: Journal Article
• Authors: Holkova, Beata; Yazbeck, Victor; Kmieciak, Maciej; Bose, Prithviraj; Ma, Shuo; Kimball, Amy; Tombes, Mary Beth; Shrader, Ellen; Wan, Wen; Weir-Wiggins, Caryn; Singh, Amanda; Hogan, Kevin T.; Conine, Sarah; Sankala, Heidi; Roberts, John D.; Shea, Thomas C.; Grant, Steven
• Is Part Of: Leukemia & lymphoma. Volume 58:Issue 6(2017)
• Page Start: 1349
• Page End: 1357
• Publication Date: 2017-06-03
• Subjects: Bortezomib -- romidepsin -- phase 1 clinical trial -- lymphoma; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2016.1276287
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m 2 bortezomib and 10 mg/m 2 romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease. The median duration of stable disease was 3.5 cycles. Correlative studies examining expression of NF-кB, XIAP, Bcl-xL, and Bim yielded variable results. The safety profile was consistent with that reported for single-agent bortezomib and romidepsin. This regimen has modest activity in heavily pretreated patients with relapsed/refractory CLL or B- or T-cell lymphoma. NCT00963274.