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

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 requir...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568356/
https://www.ncbi.nlm.nih.gov/pubmed/28830517
http://dx.doi.org/10.1186/s13063-017-2138-6
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author 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
author_facet 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
author_sort Collett, Laura
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-2138-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-55683562017-08-29 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 Trials Study Protocol 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-2138-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-22 /pmc/articles/PMC5568356/ /pubmed/28830517 http://dx.doi.org/10.1186/s13063-017-2138-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
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
Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title_full Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title_fullStr Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title_full_unstemmed Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title_short Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial
title_sort assessment of ibrutinib plus rituximab in front-line cll (flair trial): study protocol for a phase iii randomised controlled trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568356/
https://www.ncbi.nlm.nih.gov/pubmed/28830517
http://dx.doi.org/10.1186/s13063-017-2138-6
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