PURPOSE: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase 1 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. EXPERIMENTAL DESIGN: This dose-escalation study evaluated safety, pharmacokinetics and preliminary efficacy of veliparib (20-400 mg BID, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 IV, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the MTD with rituximab (375 mg/m2, day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in 7 dose escalation cohorts, and 7 patients in the dose expansion cohort. RESULTS: The MTD was veliparib 300 mg BID plus bendamustine 90 mg/m2. DLTs 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 lymphoma patients evaluable for response, 5/7 (71%) on VB and 6/7 (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response. CONCLUSION: 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.
- Received December 7, 2016.
- Revision received February 24, 2017.
- Accepted March 8, 2017.
- Copyright ©2017, American Association for Cancer Research.