REMoDL-B Trial

Trial Overview

Trial Team

Essential Trial Documentation

Publications and Presentations

Title

REMoDL-B: A Randomised Evaluation of Molecular guided therapy for Diffuse Large B-cell Lymphoma with Bortezomib

Description

REMoDL-B is a multi-centre, open label randomised trial comparing the standard care treatment of R-CHOP with R-CHOP plus bortezomib (RB-CHOP). All patients will receive one cycle of R-CHOP. They will then be randomised to receive either R-CHOP or RB-CHOP on the basis of the molecular profile of their lymphoma and the IPI score.

Objectives

Primary Objectives:

To demonstrate superior clinical efficacy, as measured by Progression-free survival (PFS), of bortezomib in combination with rituximab and CHOP (RB-CHOP) versus R-CHOP alone for the treatment of previously untreated patients with DLBCL.
To assess whether the molecular phenotype, either activated B-cell (ABC) like or germinal centre B-cell (GCB) like, of DLBCL determines the benefit from the addition of bortezomib.

Secondary Objectives:

To compare overall survival (OS) between both treatment and molecular groups
To compare event free survival (EFS) between both treatment and molecular groups
To compare disease free survival (DFS) between both treatment and molecular groups
To compare time to progression (TTP) between both treatment and molecular groups
To compare response duration (RD) between both treatment and molecular groups
To compare overall response rate (ORR) and complete response rate (CR) between both treatment groups
To assess differences in toxicity between assigned treatments
To assess quality of life and chemotherapy induced peripheral neuropathy reported by patients across the two different induction treatments
To demonstrate that accurate molecular profiling may be conducted in real-time and relate this to immunohistochemical algorithms.
To perform exploratory analysis comparing aberrations in the NF-кB pathway to clinical outcomes by treatment groups

Trial Design

Stratified open-label multicentre randomised Phase III. A novel adaptive trial design will be employed with 2 interim analysis to explore safety and efficacy in the GCB arm patients treated with RB- CHOP. Modified to randomised Phase II in ABC patients only if GCB arm closed.

Trial Status

Closed to reruitment - Currently in follow-up

Population

1132 patients with Diffuse Large B Cell Lymphoma from >50 sites throughout the UK and Switzerland.

CRUK logo

This trial is funded by an unrestricted educational grant from Janssen-Cilag, and is endorsed by Cancer Research UK (award reference no. C328/A12128)

Trial Team:

Senior Trial Manager:

Josh Caddy

Trial Co-ordinator:

Ben Lindfield

Clinical Data Coordinator:

Zoë Konn

Contact information

Email: [email protected]

SAE Reporting: [email protected]

Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. The Lancet Oncology. 2019;20(5):649-62. https://doi.org/10.1016/S1470-2045(18)30935-5

Davies AJ, Barrans S, Maishman T, Cummin TE, Bentley M, Mamot C, et al. DIFFERENTIAL EFFICACY OF BORTEZOMIB IN SUBTYPES OF DIFFUSE LARGE B-CELL LYMPHOMA (DLBL): a PROSPECTIVE RANDOMISED STUDY STRATIFIED BY TRANSCRIPTOME PROFILING: REMODL-B. Hematological Oncology. 2017;35(S2):130-1. https://doi.org/10.1002/hon.2437_120

Davies AJ, Caddy J, Maishman T, Barrans S, Mamot C, Care M, et al. A Prospective Randomised Trial of Targeted Therapy for Diffuse Large B-Cell Lymphoma (DLBCL) Based upon Real-Time Gene Expression Profiling: The Remodl-B Study of the UK NCRI and SAKK Lymphoma Groups (ISRCTN51837425). Blood. 2015;126(23):812-. https://doi.org/10.1182/blood.V126.23.812.812

Maishman T, Stanton L, Davies A, Barrans S, Worrillow L, Mamot C, et al. 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. Trials. 2013;14(1):O77. https://doi.org/10.1186/1745-6215-14-S1-O77

Sha C, Barrans S, Cucco F, Bentley MA, Care MA, Cummin T, et al. Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy. J Clin Oncol. 2019;37(3):202-12. https://doi.org/10.1200/jco.18.01314