Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)
NCT ID: NCT04546620
Last Updated: 2025-08-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE2
453 participants
INTERVENTIONAL
2021-10-19
2028-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)
NCT04529772
A Combination of Acalabrutinib With R-CHOP for Patient Diffuse Large B-cell Lymphoma (DLBCL)
NCT03571308
Acalabrutinib With DA-EPOCH-R or R-CHOP for People With Untreated Diffuse Large B-cell Lymphoma
NCT04002947
Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma
NCT05820841
Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-cell Lymphoma
NCT02285062
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
REMoDL-A is a randomised, phase II, open label, multicentre study that will be open in up to 50 centres. Up to 553 patients (453 randomised) will be recruited.
Following informed consent all patients will receive 1 cycle of conventional R-CHOP chemotherapy. At the same time the diagnostic pathology block will be sent for molecular profiling by the Haematological Malignancy Diagnostic Service (HMDS). The delivery of the first cycle of R-CHOP will allow a sufficient interval for real time determination of molecular phenotype. Patients whose biopsies yield sufficient tumour material for profiling will be randomised 2:1 in favour of the experimental arm (R-CHOP + acalabrutinib).
The primary objective will be 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A Control
6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy every 21 days.
R-CHOP
Arm A patients will receive R-CHOP alone.
Arm B Experimental
1 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.
R-CHOP + acalabrutinib
Arm B patients will receive R-CHOP in combination with acalabrutinib.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
R-CHOP
Arm A patients will receive R-CHOP alone.
R-CHOP + acalabrutinib
Arm B patients will receive R-CHOP in combination with acalabrutinib.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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.
* Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram or MUGA is required to establish baseline LVEF equal to or greater than institutional normal range.
* No concurrent uncontrolled medical condition.
* Life expectancy \> 3 months.
* Aged 16 years or above.
* Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
* Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
Exclusion Criteria
* 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.
* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
* Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
1. Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
2. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
* Women who can bear children must agree to use two highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose.
* Breastfeeding or pregnant women.
* Men who can father children must agree to use two highly effective forms of contraception with additional barrier or abstinence during the study and for 12 months after the last treatment dose.
* Men must agree to refrain from sperm donation during the study and for 12 months after the last treatment dose.
* Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent.
* Prior malignancy (other than DLBCL), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to \< 2 years.
* Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease, resection of the stomach or small bowel, partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass that would limit absorption of oral medication.
* Any immunotherapy within 4 weeks of 1st dose of the study.
* Concurrent participation in another therapeutic clinical trial.
16 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
University Hospital Southampton NHS Foundation Trust
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Andrew Davies
Role: PRINCIPAL_INVESTIGATOR
University of Southampton
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
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
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
RHM CAN1500
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.