Journal article
Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD20 lymphoid malignancies
AW Roberts, RH Advani, BS Kahl, D Persky, JW Sweetenham, DA Carney, J Yang, TB Busman, SH Enschede, RA Humerickhouse, JF Seymour
British Journal of Haematology | Published : 2015
DOI: 10.1111/bjh.13487
Abstract
The oral BCL2 inhibitor navitoclax has moderate single-agent efficacy in chronic lymphocytic leukaemia (CLL) and minor activity in lymphoma in Phase 1 trials. Navitoclax synergizes with rituximab in preclinical models of B-cell lymphoid cancers. We report the safety, pharmacokinetics and clinical activity of this combination. Patients received navitoclax (200-325 mg) daily and four standard weekly doses of rituximab. Twenty-nine patients were enrolled across three dose-escalation cohorts and a safety expansion cohort (250 mg/d navitoclax). The combination was well tolerated. Common toxicities were mild diarrhoea (79%) and nausea (72%). Grade 4 thrombocytopenia occurred in 17% of patients (do..
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Awarded by National Center for Advancing Translational Sciences
Funding Acknowledgements
We thank the trial staff and referring physicians at each of the trial sites and the patients and their families who made this study possible. Julie Dziubinski, Lura Morris, Min Tian and Joseph Beason are thanked for operational support, and Michael Brune and Teresa McNally for editorial assistance with the manuscript. All are employees of AbbVie Inc. Andrew W. Roberts has received research funding from AbbVie and Genentech and is an employee of Walter and Eliza Hall Institute of Medical Research, which receives milestone payments related to ABT-199. Ranjana H. Advani has received research funding from Genentech, is an unpaid advisor to Genentech, and her institution has received research funding from AbbVie. Brad Kahl has received research funding from AbbVie and Genentech, and is a consultant for Genentech. Daniel Persky and Dennis A. Carney have no conflicts to disclose. John W. Sweetenham indicates that his institution has received research funding from AbbVie. John F. Seymour is a consultant to and advisory board member for Roche and Genentech. Jianning Yang, Todd Busman, Sari H. Enschede, and Roderick A. Humerickhouse are AbbVie employees and may hold stock. This study was funded by AbbVie and Genentech, Inc. AWR's research was supported by the National Health and Medical Research Council of Australia (637309, 1016647, 461219), the Victorian Cancer Agency, the Australian Cancer Research Foundation, and the Leukemia and Lymphoma Society.