Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)
REMoDL-A
A Randomised Phase II Evaluation of Molecular Guided Therapy for Diffuse Large B-Cell Lymphoma With Acalabrutinib
1 other identifier
interventional
453
1 country
33
Brief Summary
This study evaluates the addition of Acalabrutinib to current standard therapy of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) for patients with previously untreated CD20 positive Diffuse Large B-cell Lymphoma (DLBCL) requiring full course chemoimmunotherapy. All patients will receive one cycle of R-CHOP. Two thirds of patients (Arm B) will go on to receive a further 5 cycles (every 21 days) of R-CHOP with Acalabrutinib. Acalabrutinib will be taken orally twice daily continuously in 21 day cycles. One third of patients (Arm A) will continue with 5 cycles of R-CHOP. Patients will be followed up initially for 24 months and then for disease status and survival until 114 progression events have been observed.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2021
Longer than P75 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 11, 2020
CompletedFirst Posted
Study publicly available on registry
September 14, 2020
CompletedStudy Start
First participant enrolled
October 19, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
April 30, 2026
April 1, 2026
6 years
August 11, 2020
April 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To establish if combining acalabrutinib with R-CHOP improves efficacy, compared to RCHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.
Progression-free survival (PFS) is defined as time from registration to progression/death from any cause.
Last patient's last follow up, approximately 4.5 years. Patients who do not experience a PFS event will be censored at the date of last follow up.
Secondary Outcomes (10)
To compare PFS between molecular groups.
Last patient's last follow-up, approximately 4.5 years.
To compare PFS between treatment groups.
Last patient's last follow-up, approximately 4.5 years.
To compare overall survival (OS) between both treatment and molecular groups.
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience an OS event will be censored at the date of last follow-up.
To compare event free survival (EFS) between both treatment and molecular groups.
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience an EFS event will be censored at the date of last follow-up.
To compare disease free survival (DFS) between both treatment and molecular groups.
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a DFS event will be censored at the date of last follow-up.
- +5 more secondary outcomes
Other Outcomes (5)
To explore correlation of molecular characteristics in tumour material to clinical outcomes.
At baseline, cycle 2 day 1, cycle 3 day 1, end of treatment and at 3, 6, 9 and 12 month follow-ups. Each cycle is 21 days.
To explore correlation of baseline PET features including tumour burden and bone marrow involvement to clinical outcomes.
Baseline and end of treatment (up to 21 weeks).
To explore combination(s) of clinical risk factors, molecular characteristics and PET features to clinical outcomes.
Baseline and end of treatment (up to 21 weeks).
- +2 more other outcomes
Study Arms (2)
Arm A Control
ACTIVE COMPARATOR6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy every 21 days.
Arm B Experimental
EXPERIMENTAL1 cycle of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy followed by 5 cycles of R-CHOP + acalabrutinib taken twice daily for 21 day cycles.
Interventions
Arm A patients will receive R-CHOP alone.
Arm B patients will receive R-CHOP in combination with acalabrutinib.
Eligibility Criteria
You may qualify if:
- Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material must be available to forward to HMDS for gene expression profiling and central pathology review. The following diagnoses by 2016 WHO classification of lymphoid neoplasms may be included:
- DLBCL, not otherwise specified (NOS)
- T-cell/histiocyte-rich large B-cell lymphoma
- Epstein-Barr virus positive DLBCL, NOS
- ALK-positive large B-cell lymphoma
- HHV8-positive DLBCL, NOS
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma)
- High-grade B-cell lymphoma, NOS
- At least one bi-dimensionally measurable lesion, defined as \>1.5 cm in its longest dimension as measured by CT.
- Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent.
- Stage IAX (bulk defined as lymph node mass \[either single or conglomerate\] diameter \>7.5cm) to stage IV disease and deemed to require a full course of chemotherapy. Patients with non-bulky IE disease will not be eligible.
- ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma.
- Adequate bone marrow function with platelets \> 100x109/L; neutrophils \> 1.0x109/L at study entry, unless lower figures are attributable to lymphoma.
- Measured or calculated creatinine clearance \> 30mls/min, (calculated using the formula of Cockcroft and Gault \[(140-Age) x Mass (kg) x (1.04 (for women) or 1.23 (for men))/Serum Creatinine (μmolL)\]).
- Serum bilirubin \< 35μmol/L and transaminases \< 1.5x upper limit of normal at time of study entry.
- +6 more criteria
You may not qualify if:
- Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.
- Patients who have received immunisation with a live vaccine within four weeks prior to enrolment will be ineligible.
- Diagnosis of primary mediastinal lymphoma.
- Diagnosis of primary Central Nervous System lymphoma or secondary CNS involvement. Those patients presenting with neurological symptoms should be investigated for CNS involvement. Routine CNS imaging or diagnostic lumbar puncture will not be required in the absence of symptoms.
- History of stroke or intracranial haemorrhage in preceding 6 months.
- History of bleeding diathesis (eg, haemophilia, von Willebrand disease).
- History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components).
- Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon) within 7 days of first dose of acalabrutinib. However patients using therapeutic low molecule weight heparin or low dose aspirin will be eligible as will those receiving direct oral anticoagulants.
- Prior exposure to an inhibitor in the BCR pathway (eg, Btk inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (eg, ABT-199).
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors should switch to short-acting H2-receptor antagonists or antacids prior to the commencement of acalabrutinib, if randomised to receive acalabrutinib.
- Active significant infection (e.g. progressive multifocal leukoencephalopathy (PML)).
- Uncontrolled autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- Major surgery in the preceding 4 weeks of first dose of acalabrutinib (if applicable). If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of acalabrutinib (if applicable).
- Corticosteroid use \>30 mg/day of prednisone or equivalent, for purposes other than for lymphoma symptom control. Patients receiving corticosteroid treatment with \<30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisone 100 mg or equivalent could be given for a maximum of 14 days as a prephase. A dose of up to 30mg or prednisolone or equivalent may be used during the screening phase to control symptoms.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital Southampton NHS Foundation Trustlead
- AstraZenecacollaborator
Study Sites (33)
Colchester General Hospital
Colchester, Essex, United Kingdom
East Kent Hospitals NHS Foundation Trust
Canterbury, Kent, United Kingdom
Monklands Hospital
Airdrie, United Kingdom
Victoria Hospital
Blackpool, United Kingdom
University Hospital Dorset NHS Foundation Trust (Bournemouth and Poole Hospitals)
Bournemouth, United Kingdom
Queens Hospital
Burton-on-Trent, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Ipswich Hospital
Ipswich, United Kingdom
St James Hospital
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Chase Farm and Barnet Hospitals
London, United Kingdom
Lewisham and Greenwich NHS Trust
London, United Kingdom
University College London Hospital
London, United Kingdom
Maidstone Hospital
Maidstone, United Kingdom
The Christie Hospital
Manchester, United Kingdom
Milton Keynes University Hospital
Milton Keynes, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Norfolk and Norwich University Hospital
Norwich, United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom
Royal Oldham Hospital
Oldham, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Queen Alexandra Hospital
Portsmouth, United Kingdom
Queen's Hospital
Romford, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Royal Stoke University Hospital
Stoke-on-Trent, United Kingdom
Singleton Hospital
Swansea, United Kingdom
Torbay Hospital
Torquay, United Kingdom
Royal Cornwall Hospital
Truro, United Kingdom
Worthing and St Richards Hospitals
Worthing, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Davies
University of Southampton
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 11, 2020
First Posted
September 14, 2020
Study Start
October 19, 2021
Primary Completion (Estimated)
November 1, 2027
Study Completion (Estimated)
May 1, 2028
Last Updated
April 30, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share