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The University of Southampton
Southampton Clinical Trials Unit

REMoDL-A

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 453 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 whose biopsies are molecularly typed GCB, ABC or Unclassifiable will be randomised.

Two thirds of patients (Arm B) will be randomised to receive a further 5 cycles (every 21 days) of R-CHOP with Acalabrutinib and one third of patients (Arm A) will be randomised to receive with 5 cycles of R-CHOP.

Recruitment is expected over 24 months with a follow-up duration of at least 2 years.

Trial Status

Open to recruitment

Population

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

Senior Trial Manager 

Joshua Caddy

Trial Manager 

Nicole Keyworth

Trial Coordinator

Tiffany Joyce

Data Manager

Nicola Scott

Clinical Data Coordinator

Robert Waugh

 

Contact Information:

Email - remodla@soton.ac.uk

SCTU fax - 0844 7740 621

 

 

SAE reporting:

Email: ctu@soton.ac.uk

Phone: 0844 7740 621

Essential Trial Documents

REMoDL-A - Protocol v3 12-May-2021

REMoDL-A - Patient Information Sheet v4 18-May-2021

REMoDL-A - Patient Information Sheet Tissue Block Screening v2 05-May-2021

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

REMoDL-A - Informed Consent Form v4 18-May-2021

REMoDL-A - Informed Consent Form Tissue Block Screening v2 05-May-2021

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

REMoDL-A - GP Letter v2 15-Jan-2021

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

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

REMoDL-A - Eligibility Checklist v2 08-Jun-2021

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

REMoDL-A - QLQ-C30 English

 

Invesigator Site Files

REMoDL-A - Investigator Site File Index v2 28-May-2021

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

REMoDL-A - Site Delegation Log v1 30-Mar-2021

REMoDL-A - Patient Screening Log v3 28-May-2021

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

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

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

REMoDL-A - PI Protocol Acknowledgement Form v1 28-May-2021

 

Pharmacy Documents

REMoDL-A - Pharmacy Manual v3 12-May-2021

REMoDL-A - Drug Order Form v2 07-Dec-2020

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 v1 09-Feb-2021

REMoDL-A - PET Acquisition Form v1 04-Feb-2021

 

Lab Documents

REMoDL-A - Lab Manual v3 14-Jan-2021

REMoDL-A - HMDS Tissue Samples Dispatch Log v3 14-Jan-2021

REMoDL-A - HMDS Sample Shipment Form v3 14-Jan-2021

 

SAE Documents

REMoDL-A - Blank SAE SUSAR form v1 23-Jul-2021

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

REMoDL-A - Acalabrutinib IB v10

REMoDL-A -Vincristine 1mgml Injection - SMPC - Feb-2020

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

REMoDL-A - Doxorubicin Hydrochloride2mgml Solutionfor Infusion - SmPC - 09-Oct-2020

REMoDL-A - MabThera Rituximab 100mg Concentrate for Solution for Infusion - SmPC

REMoDL-A - Predisolone 25mg Tablets - SmPC - 01-Nov-2019

 

Patient Registration

Link to RAVE database (patient registration and eCRF completion): https://login.imedidata.com/login

 

eCRF completion guidelines

REMoDL-A - eCRF completion guidelines v1 06-OCT-2021

 

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