A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia

Leukemia & Lymphoma
Thomas J KippsHalyna Pylypenko

Abstract

We evaluated the safety and biologic activity of the BH3 mimetic protein, navitoclax, combined with rituximab, in comparison to rituximab alone. One hundred and eighteen patients with chronic lymphocytic leukemia (CLL) were randomized to receive eight weekly doses of rituximab (arm A), eight weekly doses of rituximab plus daily navitoclax for 12 weeks (arm B) or eight weekly doses of rituximab plus daily navitoclax until disease progression or unacceptable toxicity (arm C). Investigator-assessed overall response rates (complete [CR] and partial [PR]) were 35% (arm A), 55% (arm B, p = 0.19 vs. A) and 70% (arm C, p = 0.0034 vs. A). Patients with del(17p) or high levels of BCL2 had significantly better clinical responses when treated with navitoclax. Navitoclax in combination with rituximab was well tolerated as initial therapy for patients with CLL, yielded higher response rates than rituximab alone and resulted in prolonged progression-free survival with treatment beyond 12 weeks.

References

Dec 1, 1982·American Journal of Clinical Oncology·M M OkenP P Carbone
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Oct 15, 2005·Blood·Jacques-Louis BinetUNKNOWN International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
Jan 4, 2007·The Journal of Clinical Investigation·Victoria Del Gaizo MooreAnthony Letai
May 3, 2008·Cancer Research·Christin TseSteven W Elmore
Jan 26, 2010·Cancer Chemotherapy and Pharmacology·Scott AcklerAlexander R Shoemaker
Mar 9, 2010·Gastroenterology·Takahiro KodamaNorio Hayashi
Aug 21, 2010·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Jason T RichEric W Wang
Dec 21, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew W RobertsRod Humerickhouse
Jan 12, 2012·Journal of Clinical Pharmacology·Jing LiJennifer Visich
Aug 27, 2013·Molecular Cancer Therapeutics·Christian Billard
Sep 10, 2013·Advances in Experimental Medicine and Biology·Chris Fegan, Chris Pepper
Nov 12, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Edna F ChooRichard Voorman
Jan 29, 2014·British Journal of Haematology·Benjamin T Kile

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Citations

Oct 28, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Beata ŻołnowskaKrzysztof Szafrański
Dec 26, 2015·Mitochondrion·Bing YanJiri Neuzil
Nov 3, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R StauderV Goede
Feb 18, 2017·Nature Reviews. Drug Discovery·Avi AshkenaziAndrew J Souers
Jan 25, 2017·Current Hematologic Malignancy Reports·Benjamin L Lampson, Matthew S Davids
Apr 28, 2017·British Journal of Haematology·Meike VoglerMartin J S Dyer
Dec 20, 2016·Anais Da Academia Brasileira De Ciências·João M A DelouHelena L Borges
Oct 4, 2016·Therapeutic Advances in Hematology·Gilad Itchaki, Jennifer R Brown
Dec 3, 2016·Therapeutic Advances in Hematology·Valentín Ortíz-MaldonadoJulio Delgado
Mar 24, 2018·International Journal of Molecular Sciences·Lidia VillanovaMicol E Fiori
Oct 7, 2017·Advances in Therapy·Gilles SallesDavid G Maloney
Sep 26, 2017·Expert Opinion on Investigational Drugs·Pawel Robak, Tadeusz Robak
Oct 28, 2017·Cell Death and Differentiation·Joan Montero, Antony Letai
May 31, 2018·Medicinal Research Reviews·Ahmet Can TimucinOzgur Kutuk
Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stephani Joy Y MacalinoSun Choi
Dec 19, 2016·F1000Research·Haiming DaiScott H Kaufmann
Apr 11, 2019·Expert Opinion on Drug Metabolism & Toxicology·Anna Korycka-WolowiecTadeusz Robak
Apr 3, 2019·Critical Reviews in Clinical Laboratory Sciences·Cristina BagaceanYves Renaudineau
May 12, 2018·Journal of Hematology & Oncology·Guilherme Fleury PeriniNelson Hamerschlak
Jul 21, 2017·Blood·Matthew S Davids
Sep 13, 2019·Current Hematologic Malignancy Reports·Herbert Eradat
Mar 24, 2020·Nature Reviews. Clinical Oncology·Benedito A Carneiro, Wafik S El-Deiry
Apr 7, 2016·Oncotarget·Jiusheng DengXingming Deng
Apr 17, 2018·International Journal of Oncology·Toshiyuki SumiYuji Sakuma
Jul 30, 2019·Frontiers in Pharmacology·Sebastian N KnoppertLucas L Falke
Oct 31, 2019·BioMed Research International·Zeping HanJinhua He
Feb 7, 2020·Current Oncology Reports·Annika Scheffold, Stephan Stilgenbauer
Apr 16, 2020·Cancers·Magdalena Klanova, Pavel Klener
Jul 24, 2020·Expert Review of Hematology·Candida Vitale, Alessandra Ferrajoli
Apr 14, 2016·Biochemical Society Transactions·Hannah Karlsson
Jan 29, 2020·Current Oncology Reports·Luke FletcherAlexey Danilov
Nov 15, 2019·HemaSphere·Deyan Y YosifovDaniel Mertens
May 27, 2020·British Journal of Haematology·Paraskevi DiamantiAllison Blair
Oct 25, 2017·The Biochemical Journal·Astrid Ruefli-Brasse, John C Reed

❮ Previous
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