Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial
| Autor: | Eugen Tausch, Marco Montillo, Lukas Smolej, David Simpson, Árpád Illés, Franck Morschhauser, Yeonhee Kim, Jacqueline C. Barrientos, Paolo Ghia, Peter Hillmen, Miklos Egyed, Paula Marlton, Tadeusz Robak, Jeff P. Sharman, Julio Delgado, Andrew D. Zelenetz, Adeboye H. Adewoye, Jennifer R. Brown, Alexander S. Pristupa, Wojciech Jurczak, Lyndah Dreiling, Stephan Stilgenbauer, Bertrand Coiffier |
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| Přispěvatelé: | Memorial Sloane Kettering Cancer Center [New York], Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], University of Debrecen Egyetem [Debrecen], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Medical University of Łódź (MUL), University of Ulm (UUlm), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Zelenetz, Andrew D, Barrientos, Jacqueline C, Brown, Jennifer R, Coiffier, Bertrand, Delgado, Julio, Egyed, Mikló, Ghia, PAOLO PROSPERO, Illés, Árpád, Jurczak, Wojciech, Marlton, Paula, Montillo, Marco, Morschhauser, Franck, Pristupa, Alexander S, Robak, Tadeusz, Sharman, Jeff P, Simpson, David, Smolej, Lukáš, Tausch, Eugen, Adewoye, Adeboye H, Dreiling, Lyndah K, Kim, Yeonhee, Stilgenbauer, Stephan, Hillmen, Peter, Université de Lille, CHU Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Barcelona Centre for International Health Research, Hospital Clinic [CRESIB], Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Medical University of Łódź [MUL] |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Bendamustine
Adult Male medicine.medical_specialty [SDV]Life Sciences [q-bio] Population Placebo-controlled study Placebo Klinikai orvostudományok 03 medical and health sciences 0302 clinical medicine Double-Blind Method Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Bendamustine Hydrochloride Humans education Survival rate Aged Neoplasm Staging Quinazolinones Salvage Therapy education.field_of_study business.industry Orvostudományok Middle Aged medicine.disease Prognosis Leukemia Lymphocytic Chronic B-Cell 3. Good health Surgery Survival Rate Oncology Drug Resistance Neoplasm Purines 030220 oncology & carcinogenesis Rituximab Female Neoplasm Recurrence Local Idelalisib business Febrile neutropenia 030215 immunology medicine.drug Follow-Up Studies |
| Zdroj: | Lancet Oncology Lancet Oncology, 2017, The Lancet Oncology, 18 (3), pp.297-311. ⟨10.1016/S1470-2045(16)30671-4⟩ |
| ISSN: | 0156-9295 1470-2045 1474-5488 |
| Popis: | International audience; BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled. Patients were randomly assigned (1:1) by a central interactive web response system to receive bendamustine plus rituximab for a maximum of six cycles (bendamustine: 70 mg/m2 intravenously on days 1 and 2 for six 28-day cycles; rituximab: 375 mg/m2 on day 1 of cycle 1, and 500 mg/m2 on day 1 of cycles 2-6) in addition to either twice-daily oral idelalisib (150 mg) or placebo until disease progression or intolerable study drug-related toxicity. Randomisation was stratified by high-risk features (IGHV, del[17p], or TP53 mutation) and refractory versus relapsed disease. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat population. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01569295. FINDINGS: Between June 26, 2012, and Aug 21, 2014, 416 patients were enrolled and randomly assigned to the idelalisib (n=207) and placebo (n=209) groups. At a median follow-up of 14 months (IQR 7-18), median progression-free survival was 20·8 months (95% CI 16·6-26·4) in the idelalisib group and 11·1 months (8·9-11·1) in the placebo group (hazard ratio [HR] 0·33, 95% CI 0·25-0·44; p |
| Databáze: | OpenAIRE |
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