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) versusÌý 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 randomisedÌýPhase 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
Population
1132 patients with Diffuse Large B Cell Lymphoma from >50 sites throughout the UK and Switzerland.
Contact Details
All trial enquiries should be sent to ctuadmin@soton.ac.uk
Publications
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.Ìý
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.Ìý
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-.Ìý
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.Ìý
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.Ìý
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This trial was funded by an unrestricted educational grant from Janssen-Cilag, and endorsed by Cancer Research UK (award reference no. C328/A12128)