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Leukemia & Lymphoma Volume 57, 2016 - Issue 3
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Original Articles: Clinical

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

Beata HolkovaMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA, ;Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA, Correspondence[email protected]
,
Maciej KmieciakMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Prithviraj BoseUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA,
,
Victor Y. YazbeckMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA, ;Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA,
,
Paul M. BarrJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA,
,
Mary Beth TombesMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Ellen ShraderMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Caryn Weir-WigginsMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
April D. RollinsMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Erin M. CebulaJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA,
,
Emily PierceJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA,
,
Megan HerrJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA,
,
Heidi SankalaMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Kevin T. HoganMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA,
,
Wen WanDepartment of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA,
,
Changyong FengJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA, ;Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA,
,
Derick R. PetersonDepartment of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA,
,
Richard I. FisherFox Chase Cancer Center, Temple Health, Philadelphia, PA, USA,
,
Steven GrantMassey Cancer Center and Virginia Commonwealth University, Richmond, VA, USA, ;Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA, ;Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA, ;Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA, ;The Institute for Molecular Medicine, Virginia Commonwealth University, Richmond, VA, USA, and
&
Jonathan W. FriedbergJames P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA, ;Department of Medicine, University of Rochester, Rochester, NY, USA
 show all
Pages 635-643 | Received 17 Mar 2015, Accepted 16 Jul 2015, Published online: 12 Oct 2015
 
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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.

Acknowledgements

The study was supported by grants from the National Institutes of Health (NCI R01 CA93738, NCI R01 CA100866, NCI R21 CA110953, NCI R01 CA167708, NCI P50 CA130805 [Lymphoma SPORE], NCI P30 CA016059 [Cancer Center Support Grant to the Virginia Commonwealth (VCU) Massey Cancer Center (MCC) supported, in part, the use of the VCU MCC Biostatistics Shared Resource], and UL1TR000058 [CTSA award to VCU from NCATS/NIH]) and an award from the Multiple Myeloma Research Foundation.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Supplementary materials available online

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