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Navitoclax synergizes with rituximab in preclinical models of B\u2010cell lymphoid cancers. We report the safety, pharmacokinetics and clinical activity of this combination. Patients received navitoclax (200\u2013325\u00a0mg) daily and four standard weekly doses of rituximab. Twenty\u2010nine patients were enrolled across three dose\u2010escalation cohorts and a safety expansion cohort (250\u00a0mg\/d navitoclax). The combination was well tolerated. Common toxicities were mild diarrhoea (79%) and nausea (72%). Grade 4 thrombocytopenia occurred in 17% of patients (dose limiting at 325\u00a0mg\/d). <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19<jats:sup>+<\/jats:sup> counts were severely reduced, while <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3<jats:sup>+<\/jats:sup> cells (<jats:italic>~<\/jats:italic> 20%) and serum immunoglobulin M levels (<jats:italic>~<\/jats:italic> 33%) were also reduced during the first year. The maximum tolerated dose for navitoclax in combination was 250\u00a0mg\/d. Pharmacokinetic analyses revealed no apparent interactions between the drugs. The response rate in patients with follicular lymphoma was 9\/12, including five complete responses. All five patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>\/small lymphocytic leukaemia achieved partial responses. One of nine patients with aggressive lymphoma responded. The addition of rituximab to navitoclax 250\u00a0mg\/d is safe; the combination demonstrates higher response rates for low\u2010grade lymphoid cancers than observed for either agent alone in previous Phase 1 trials.<\/jats:p>","DOI":"10.1111\/bjh.13487","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T03:59:03Z","timestamp":1430884743000},"page":"669-678","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the <scp>BCL<\/scp>2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory <scp>CD<\/scp>20<sup>+<\/sup> lymphoid malignancies"],"prefix":"10.1111","volume":"170","author":[{"given":"Andrew W.","family":"Roberts","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology and BMT The Royal Melbourne Hospital Parkville Vic. Australia"},{"name":"Division of Cancer and Haematology The Walter and Eliza Hall Institute of Medical Research Parkville Vic. Australia"},{"name":"Victorian Comprehensive Cancer Centre Parkville Vic. Australia"},{"name":"Faculty of Medicine University of Melbourne Parkville Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjana H.","family":"Advani","sequence":"additional","affiliation":[{"name":"Stanford University Medical Center Stanford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad S.","family":"Kahl","sequence":"additional","affiliation":[{"name":"University of Wisconsin Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Persky","sequence":"additional","affiliation":[{"name":"University of Arizona Cancer Center Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Sweetenham","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Carney","sequence":"additional","affiliation":[{"name":"Victorian Comprehensive Cancer Centre Parkville Vic. Australia"},{"name":"Faculty of Medicine University of Melbourne Parkville Vic. Australia"},{"name":"Division of Cancer Medicine Peter MacCallum Cancer Centre Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Yang","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd B.","family":"Busman","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari H.","family":"Enschede","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick A.","family":"Humerickhouse","sequence":"additional","affiliation":[{"name":"AbbVie Inc. 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