The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma

Jacob D Soumerai; Andrew D Zelenetz; Craig H Moskowitz; M Lia Palomba; Paul A Hamlin, Jr; Ariela Noy; David J Straus; Alison J Moskowitz; Anas Younes; Matthew J Matasar; Steven M Horwitz; Carol S Portlock; Jason A Konner; Mrinal M Gounder; David M Hyman; Martin H Voss; Matthew G Fury; Devika Gajria; Richard D Carvajal; Alan L Ho; Jan H Beumer; Brian Kiesel; Zhigang Zhang; Alice Chen; Richard F Little; Christine Jarjies; Thu O Dang; Fallon France; Nishant Mishra; John F Gerecitano

doi:10.1158/1078-0432.CCR-16-3068

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The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma

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The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma

Jacob D Soumerai, Andrew D Zelenetz, Craig H Moskowitz, M Lia Palomba, Paul A Hamlin, Jr, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, …

Clinical cancer research, Vol.23(15), pp.4119-4126

2017-08-01

DOI: https://doi.org/10.1158/1078-0432.CCR-16-3068

PMCID: PMC5541854

PMID: 28314788

Abstract

The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20-400 mg twice a day, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m , day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort. The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response. VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702 .

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.130 Lymphomas; 1.130.132 Lymphoma
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
Creators: Jacob D Soumerai - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York. soumeraj@mskcc.org
Andrew D Zelenetz - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Craig H Moskowitz - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York
M Lia Palomba - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Paul A Hamlin, Jr - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Ariela Noy - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
David J Straus - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Alison J Moskowitz - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Anas Younes - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Matthew J Matasar - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York
Steven M Horwitz - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Carol S Portlock - Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
Jason A Konner - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Mrinal M Gounder - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
David M Hyman - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Martin H Voss - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Matthew G Fury - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Devika Gajria - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Richard D Carvajal - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Alan L Ho - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Jan H Beumer - Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Brian Kiesel - Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
Zhigang Zhang - Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
Alice Chen - Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, Maryland
Richard F Little - Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, Maryland
Christine Jarjies - Memorial Sloan Kettering Cancer Center, New York, New York
Thu O Dang - Memorial Sloan Kettering Cancer Center, New York, New York
Fallon France - Memorial Sloan Kettering Cancer Center, New York, New York
Nishant Mishra - Memorial Sloan Kettering Cancer Center, New York, New York
John F Gerecitano - Department of Medicine, Center for Developmental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York
Publication Details: Clinical cancer research, Vol.23(15), pp.4119-4126
Grant note: P30 CA047904 / NCI NIH HHS UM1 CA186690 / NCI NIH HHS P30 CA008748 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Medicine
Language: English
Resource Type: Journal article
PMID: 28314788
PMCID: PMC5541854
Record Identifier: 991031615346802976