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The University of Southampton
Southampton Clinical Trials Unit


Trial Title

A randomised Phase II Evaluation of Molecular Guided Therapy for Diffuse Large B-Cell Lymphoma with Acalabrutinib (REMoDL-A).

Trial Description

Retrospective molecular profiling of untreated DLBCL samples has recognised 4 distinct sub-classifications of this disease (ABC-DLBCL, GCB- DLBCL, unclassified DLBCL and MHG DLBCL), each with unique biological features and clinical outcomes when treated with CHOP or R-CHOP chemotherapy. Dysregulation of B-cell receptors (BCR) signalling pathway is observed in ABC type and requires Bruton tyrosine kinase (Btk) activation. Clinical studies have shown that targeting BCR signalling pathway by the inhibition of Btk with ibrutinib (a 1st generation Btk inhibitor) in combination with R-CHOP chemotherapy for previously untreated B-cell non Hodgkin lymphoma is safe. Acalabrutinib is a 2nd generation Btk inhibitor with increased target selectivity compared to ibrutinib. It is postulated that the addition of acalabrutinib to R-CHOP chemotherapy may improve tumour response compared to ibrutinib + R-CHOP.

REMoDL-A is an open label randomised phase II trial examining efficacy of combined R-CHOP and acalabrutinib chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) compared to R-CHOP alone.

Trial Objectives 

Primary Objective:

To establish if combining acalabrutinib with R-CHOP improves efficacy, compared to R-CHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.

Secondary Objectives:

·         To compare progression free survival between both treatment and molecular groups.

·         To compare overall survival between both treatment and molecular groups.

·         To compare event free survival between both treatment and molecular groups.

·         To compare time to treatment failure between both treatment and molecular groups.

·         To compare disease free survival between both treatment and molecular groups.

·         To compare time to progression between both treatment and molecular groups.

·         To compare response duration between both treatment and molecular groups.

·         To compare overall response rate and complete response rate between both treatment groups.

·         To assess differences in toxicity between assigned treatments.

·         To assess differences in quality of life in different treatment arms.

Tertiary Objectives

·         To explore correlation of baseline PET features including metabolic tumour volume (MTV), tumour lesion glycolysis (TLG), extranodal sites and bone marrow involvement with clinical risk factor and molecular characteristics in tumour material.

·         To compare metabolic response rates between molecular groups.

·         To explore correlation of molecular characteristics in tumour material to clinical outcomes.

Trial Design

This is a multicentre, stratified, open-label, randomised phase II trial.

We aim to recruit approximately 375 patients. This study will have two treatment arms.

Following informed consent, all patients will receive one cycle of R-CHOP. At the same time, the diagnostic pathology block will be sent for molecular profiling and assignment of subtype to GCB, ABC, Unclassifiable, MHG or failed RNA extraction.

Patients with an International Prognostic Index (IPI) of 0-1 will be randomised between Arm A (R-CHOP only for a further 5 cycles) and Arm B (R-CHOP + acalabrutinib for a further 5 cycles), with treatment cycles lasting 21 days. Two thirds of patients who are randomised will be assigned to Arm B, and one third will be randomised to Arm A.

Patients with an IPI of 2-5 will be allocated to Arm B without randomisation and receive R-CHOP + acalabrutinib for the remaining 5 cycles.

Recruitment is expected over 39 months with a follow-up duration of at least 2 years.

Trial Status

Open to recruitment


Patients aged ≥ 16 years with previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL) requiring full course chemoimmunotherapy.


CRUK and NIHR logo

This trial is funded by an unrestricted educational grant from AstraZeneca and is endorsed by Cancer Research UK (award reference no. C30423/A29680) with support from the NIHR.

Senior Trial Manager 

Nicole Keyworth

Trial Manager 

Tiffany Joyce

Trial Coordinator

Ben Lindfield

Data Manager

Zoe Konn

Data Manager

Robert Waugh

Clinical Data Coordinator

Oli Seymour

Clinical Trial Monitors:

Amy Jones


Contact Information:

Email -

SAE reporting:



Essential Trial Documents

REMoDL-A - Protocol v5 11-Oct-2023

REMoDL-A - Patient Information Sheet - v6 22-Aug-2023

REMoDL-A - Patient Information Sheet Tissue Block Screening - v3 22-Aug-2023

REMoDL-A - Pregnant Partner Patient Information Sheet v2 05-May-2021

REMoDL-A - Informed Consent Form v6 22-Aug-2023

REMoDL-A - Informed Consent Form Tissue Block Screening Consent v3 22-Aug-2023

REMoDL-A - Pregnant Partner Informed Consent Formt v2 05-May-2021

REMoDL-A - GP letter v4 22-Aug-2023

REMoDL-A - Patient Diary v2 22-Jan-2021

REMoDL-A - Patient Information Card v2 07-Dec 2020

REMoDL-A - Eligibility Checklist v5 15-Nov-2023

REMoDL-A - FACT-Lym ENG Final v4 16-Nov-2007

REMoDL-A - QLQ-C30 English


Investigator Site Files

REMoDL-A - Investigator Site File Index v3 06-Jul-2021

REMoDL-A - Study Contacts and Information Page v1 28-May-2021

REMoDL-A - Site Delegation Log v2 25-Nov-2021

REMoDL-A - Screening Log v4 23-Nov-2023

REMoDL-A - Master Patient List v2 07-Dec 2020

REMoDL-A - Training Log v3 15-Nov-2023

REMoDL-A - Site Visit Log v2 07-Dec-2020

REMoDL-A - PI Protocol Acknowledgement Form v3 27-Oct-2023


Pharmacy Documents

REMoDL-A - Pharmacy Manual v5 08-Nov-2023

REMoDL-A Drug Order Form v3 03-Dec-2021

REMoDL-A - Acalabrutinib Accountability Log v3 02-Feb-2021

REMoDL-A - Acalabrutinib Subject Dispensing Log v3 02-Feb-2021

REMoDL-A - R-CHOP Drug Dispensing Log v2 29-Jan-2021

REMoDL-A - Pharmacy Site File Index v1 27-Jan-2021


Imaging Documents

REMoDL-A - Imaging Manual v3 08-Nov-2023

REMoDL-A - PET Acquisition Form v2 18-Jan-2022


Lab Documents

REMoDL-A - Lab Manual v6 08-Nov-2023

REMoDL-A - HMDS Tissue Samples Dispatch Log v4 20-Jan-2023

REMoDL-A - HMDS Sample Shipment Form v6 25-Oct-2023


SAE Documents

REMoDL-A Blank SAE SUSAR Form v2 10-May-2022

REMoDL-A - Instructions for adverse and serious adverse event reporting v1 27-Jan-2021

REMoDL-A - Acalabrutinib IB Edition 12

REMoDL-A - Vincristine Sulphate 1 mgml Injection - SmPC - 14-Mar-2023

REMoDL-A - Cyclophosphamide Injection500mg - SmPC - 07-Jun-2016

REMoDL-A - Doxorubicin Hydrochloride 2mgml Solution for Infusion - SmPC - 17-May-2023

REMoDL-A - MabThera 100mg Concentrate for Solution - SmPC - Oct 2021

REMoDL-A - Prednisolone 25mg Tablets - SmPC - 23-Mar-2023


Patient Registration

Link to RAVE database (patient registration and eCRF completion):


eCRF completion guidelines

REMoDL-A - eCRF Completion Guidance v3 12-Dec-2023


Press releases, video clips and other external websites

(University of Southampton cannot accept responsibility for external websites)


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