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Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.
Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P.
Afiliación
  • Byrd JC; Division of Hematology and Comprehensive Cancer Center and Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH;
  • Flynn JM; Division of Hematology and Comprehensive Cancer Center and.
  • Kipps TJ; Moores Cancer Center, University of California San Diego, La Jolla, CA;
  • Boxer M; Arizona Oncology Associates, Tucson, AZ; US Oncology Research, Vancouver, WA;
  • Kolibaba KS; US Oncology Research, Vancouver, WA; Northwest Cancer Specialists, Vancouver, WA;
  • Carlile DJ; Roche Innovation Center, Welwyn Garden City, United Kingdom;
  • Fingerle-Rowson G; F. Hoffmann-La Roche, Pharma Development Oncology, Basel, Switzerland;
  • Tyson N; F. Hoffmann-La Roche Ltd., Welwyn Garden City, United Kingdom;
  • Hirata J; Genentech Inc., South San Francisco, CA; and.
  • Sharman JP; US Oncology Research, Vancouver, WA; Willamette Valley Cancer Institute and Research Center, Eugene, OR.
Blood ; 127(1): 79-86, 2016 Jan 07.
Article en En | MEDLINE | ID: mdl-26472752
Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Anticuerpos Monoclonales Humanizados / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Anticuerpos Monoclonales Humanizados / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos