A novel adaptive trial design: randomised evaluation of molecular guided therapy for diffuse large b-cell lymphoma with bortezomib (REMODL-B) with two interim analyses to explore safety and efficacy

Tom Maishman,Matt Care,Tikki Immins,Andrew Mcmillan,Sharon Barrans,Peter Johnson,Lisa Worrillow,Andy Davies,Debbie Hamid,Paul Fields,Louise Stanton,Christoph Mamot,Andrew Jack

doi:10.1186/1745-6215-14-s1-o77

Abstract

Methods The trial uses an adaptive design and aims to recruit 940 patients across 100 sites in the UK and Switzerland (currently recruited 398 patients). After being profiled within real time (during cycle 1), ABC, GCB and unclassifiable molecular phenotype patients are randomised to receive RB-CHOP or R-CHOP with equal allocation. Two interim analyses will be carried out to stop the good prognosis GCB group early if required using a Case Morgan [1] analysis: (i) The first will be a safety analysis performed after the first 55 GCB RB-CHOP patients have been followed for 6 months. If 6 month PFS<80%, the GCB group will close. (ii) The second will be for futility in the GCB group and performed after the first 73 GCB RB-CHOP patients have been followed for 1 year. If 1 year PFS<85%, the GCB group will close. If the GCB group closes the trial will then be modified to a randomised Phase II trial in ABC patients and sample size calculations will be revised.

Highlights

Retrospective molecular profiling of untreated Diffuse Large B-Cell Lymphoma (DLBCL) samples has recognised distinct sub-classifications of this disease, each with unique biological features and clinical outcomes
(ii) To assess whether the molecular phenotype determines benefit from the addition of bortezomib
Two interim analyses will be carried out to stop the good prognosis GCB group early if required using a Case Morgan [1] analysis: (i) The first will be a safety analysis performed after the first 55 GCB rituximab and CHOP (RB-CHOP) patients have been followed for 6 months

Summary

Open Access

A novel adaptive trial design: randomised evaluation of molecular guided therapy for diffuse large b-cell lymphoma with bortezomib (REMODL-B) with two interim analyses to explore safety and efficacy. Tom Maishman1*, Louise Stanton, Andy Davies, Sharon Barrans, Lisa Worrillow, Christoph Mamot, Matt Care, Tikki Immins, Debbie Hamid, Andrew McMillan, Paul Fields, Andrew Jack, Peter Johnson. From 2nd Clinical Trials Methodology Conference: Methodology Matters Edinburgh, UK. From 2nd Clinical Trials Methodology Conference: Methodology Matters Edinburgh, UK. 18-19 November 2013

Background

Methods