Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial

Collett, Laura; Howard, Dena R.; Munir, Talha; McParland, Lucy; Oughton, Jamie B.; Rawstron, Andy C.; Hockaday, Anna; Dimbleby, Claire; Phillips, David; McMahon, Kathryn; Hulme, Claire; Allsup, David; Bloor, Adrian; Hillmen, Peter

Abstract

Background
Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS).

Methods/design
FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness.

Discussion
The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable.

Trial registration
ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013.

Citation

Collett, L., Howard, D. R., Munir, T., McParland, L., Oughton, J. B., Rawstron, A. C., Hockaday, A., Dimbleby, C., Phillips, D., McMahon, K., Hulme, C., Allsup, D., Bloor, A., & Hillmen, P. (2017). Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial. Trials, 18(1), Article 387. https://doi.org/10.1186/s13063-017-2138-6

• Journal Article Type: Article
• Acceptance Date: Nov 3, 2016
• Online Publication Date: Aug 22, 2017
• Publication Date: Aug 22, 2017
• Deposit Date: Mar 22, 2018
• Publicly Available Date: Mar 29, 2018
• Journal: Trials
• Print ISSN: 1745-6215
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: 1
• Article Number: 387
• DOI: https://doi.org/10.1186/s13063-017-2138-6
• Keywords: Medicine (miscellaneous); Pharmacology (medical)
• Public URL: https://hull-repository.worktribe.com/output/752047
• Publisher URL: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2138-6
• Contract Date: Mar 22, 2018