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Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial

McIlroy, Graham; Lax, Siân; Gaskell, Charlotte; Jackson, Aimee; Rhodes, Malcolm; Seale, Tania; Fox; Hopkins, Lousie; Okosun, Jessica; Barrington, Sally F; Ringshausen, Ingo; Ramsay, Alan G; Calaminici; Linton, Kim; Bishton, Mark

Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial Thumbnail


Authors

Graham McIlroy

Siân Lax

Charlotte Gaskell

Aimee Jackson

Malcolm Rhodes

Tania Seale

Fox

Lousie Hopkins

Jessica Okosun

Sally F Barrington

Ingo Ringshausen

Alan G Ramsay

Calaminici

Kim Linton

Mark Bishton



Abstract

Background
Relapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined.

Methods
The REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms.

Discussion:
Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery.

Trial registration: ClinicalTrials.gov: NCT05848765; 08-May-2023. EudraCT: 2022-000677-75; 10-Feb-2022.

Citation

McIlroy, G., Lax, S., Gaskell, C., Jackson, A., Rhodes, M., Seale, T., …Bishton, M. (2024). Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial. BMC Cancer, 24, Article 370. https://doi.org/10.1186/s12885-024-12112-0

Journal Article Type Article
Acceptance Date Mar 12, 2024
Online Publication Date Mar 25, 2024
Publication Date Mar 25, 2024
Deposit Date Mar 19, 2024
Publicly Available Date Mar 25, 2024
Journal BMC Cancer
Electronic ISSN 1471-2407
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 24
Article Number 370
DOI https://doi.org/10.1186/s12885-024-12112-0
Keywords Relapsed follicular lymphoma, Adaptive design, Lenalidomide, Bayesian power prior methodology, Clinical trial, Epcoritamab
Public URL https://nottingham-repository.worktribe.com/output/32743913
Publisher URL https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12112-0

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