Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial.
Abstract | BACKGROUND: METHODS: iLLUMINATE is a multicentre, randomised, open-label, phase 3 trial done at 74 academic and community hospitals in Australia, Canada, Israel, New Zealand, Russia, Turkey, the EU, and the USA in patients with previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma, either aged 65 years or older or younger than 65 years with coexisting conditions. Patients were randomly assigned (1:1) using a blocked randomisation schedule, stratified by Eastern Cooperative Oncology Group performance status and cytogenetics, to receive ibrutinib plus obinutuzumab (oral ibrutinib [420 mg once daily continuously] combined with intravenous obinutuzumab [100 mg on day 1, 900 mg on day 2, 1000 mg on day 8, and 1000 mg on day 15 of cycle 1 and on day 1 of subsequent 28-day cycles, for a total of six cycles]) or chlorambucil plus obinutuzumab (oral chlorambucil [0·5 mg/kg bodyweight on days 1 and 15 of each 28-day cycle for six cycles] combined with the same obinutuzumab regimen). Allocation concealment was achieved using an interactive web response system. Patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival assessed by a masked independent review committee in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov (NCT02264574), and patient enrolment is complete. FINDINGS: INTERPRETATION:
Ibrutinib plus obinutuzumab is an efficacious and safe chemotherapy-free combination treatment in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma independent of high-risk features and provides an alternative first-line treatment option for these patients. FUNDING: Pharmacyclics LLC, an AbbVie Company, and Janssen Research and Development.
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Authors | Carol Moreno, Richard Greil, Fatih Demirkan, Alessandra Tedeschi, Bertrand Anz, Loree Larratt, Martin Simkovic, Olga Samoilova, Jan Novak, Dina Ben-Yehuda, Vladimir Strugov, Devinder Gill, John G Gribben, Emily Hsu, Chih-Jian Lih, Cathy Zhou, Fong Clow, Danelle F James, Lori Styles, Ian W Flinn |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 20
Issue 1
Pg. 43-56
(01 2019)
ISSN: 1474-5488 [Electronic] England |
PMID | 30522969
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Piperidines
- Pyrazoles
- Pyrimidines
- Chlorambucil
- ibrutinib
- Adenine
- obinutuzumab
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Topics |
- Adenine
(analogs & derivatives)
- Aged
- Antibodies, Monoclonal, Humanized
(administration & dosage, adverse effects, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects, therapeutic use)
- Chlorambucil
(administration & dosage, adverse effects, therapeutic use)
- Female
- Humans
- Intention to Treat Analysis
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy, mortality)
- Male
- Piperidines
- Progression-Free Survival
- Pyrazoles
(administration & dosage, adverse effects, therapeutic use)
- Pyrimidines
(administration & dosage, adverse effects, therapeutic use)
- Treatment Outcome
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