title: 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.
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.
authors: a Department of Hematology-Oncology , UCSD School of Medicine , San Diego , CA , USA.
authors: Thomas J
authors: TJ
authors: Kipps
authors: b Division of Hematology-Oncology, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA.
authors: Herbert
authors: H
authors: Eradat
authors: c Department of Hematology , Community Hospitals , Chorzow , Poland.
authors: Sebastian
authors: S
authors: Grosicki
authors: d Frankston Hospital and Monash University , Frankston , Australia.
authors: John
authors: J
authors: Catalano
authors: e John Fawkner Cancer Trial Centre , Coburg , Australia.
authors: Walter
authors: W
authors: Cosolo
authors: f Department of Hematology , National Research Center for Radiation Medicine of National Medical Academy of Sciences of Ukraine , Kyiv , Ukraine.
authors: Iryna S
authors: IS
authors: Dyagil
authors: g Genentech, Inc. , South San Francisco , CA , USA.
authors: Sreeni
authors: S
authors: Yalamanchili
authors: g Genentech, Inc. , South San Francisco , CA , USA.
authors: Akiko
authors: A
authors: Chai
authors: g Genentech, Inc. , South San Francisco , CA , USA.
authors: Srikumar
authors: S
authors: Sahasranaman
authors: g Genentech, Inc. , South San Francisco , CA , USA.
authors: Elizabeth
authors: E
authors: Punnoose
authors: g Genentech, Inc. , South San Francisco , CA , USA.
authors: Deborah
authors: D
authors: Hurst
authors: h Department of Hematology , Cherkassy Regional Oncological Center , Cherkassy , Ukraine.
authors: Halyna
authors: H
authors: Pylypenko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069283:Rituximab / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D000069283:Rituximab; C528561:navitoclax
keywords: ABT-263; B-cell; BCL2; BH3; chronic lymphocytic leukemia; clinical trial; navitoclax; rituximab