TY - JOUR
T1 - Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT)
T2 - study protocol for a multi-centre, open-label, randomised, phase II platform trial
AU - McIlroy, Graham
AU - Lax, Siân
AU - Gaskell, Charlotte
AU - Jackson, Aimee
AU - Rhodes, Malcolm
AU - Seale, Tania
AU - Fox, Sonia
AU - Hopkins, Lousie
AU - Okosun, Jessica
AU - Barrington, Sally F.
AU - Ringshausen, Ingo
AU - Ramsay, Alan G.
AU - Calaminici, Maria
AU - Linton, Kim
AU - Bishton, Mark
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Adaptive design
KW - Bayesian power prior methodology
KW - Clinical trial
KW - Epcoritamab
KW - Lenalidomide
KW - Relapsed follicular lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85188509926&partnerID=8YFLogxK
U2 - 10.1186/s12885-024-12112-0
DO - 10.1186/s12885-024-12112-0
M3 - Article
C2 - 38528445
AN - SCOPUS:85188509926
SN - 1471-2407
VL - 24
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 370
ER -
