AzTrials
AzTrials

Diffuse Large B Cell LymphomaPhase 2REMoDL-ANCT04546620

Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)

A Phase 2 study testing R-CHOP and R-CHOP + acalabrutinib in people with Diffuse Large B Cell Lymphoma, run by University Hospital Southampton NHS Foundation Trust at 33 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Diffuse Large B Cell Lymphoma
What is being tested?
R-CHOP and R-CHOP + acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
453 participants
Where
33 sitesUnited Kingdom
Study dates
19 Oct 2021to May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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.

Who cannot join

  • 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).
Show all 28Show fewer
  • 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.
  • 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.
  • 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.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United Kingdom33 sites

  • Monklands Hospital

    Airdrie

  • Victoria Hospital

    Blackpool

  • University Hospital Dorset NHS Foundation Trust (Bournemouth and Poole Hospitals)

    Bournemouth

  • Queens Hospital

    Burton-on-Trent

  • Addenbrooke's Hospital

    Cambridge

  • East Kent Hospitals NHS Foundation Trust

    Canterbury, Kent

  • Colchester General Hospital

    Colchester, Essex

  • Royal Derby Hospital

    Derby

  • Royal Devon and Exeter Hospital

    Exeter

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Ipswich Hospital

    Ipswich

  • St James Hospital

    Leeds

  • Leicester Royal Infirmary

    Leicester

  • Chase Farm and Barnet Hospitals

    London

  • Lewisham and Greenwich NHS Trust

    London

  • University College London Hospital

    London

  • Maidstone Hospital

    Maidstone

  • The Christie Hospital

    Manchester

  • Milton Keynes University Hospital

    Milton Keynes

  • Freeman Hospital

    Newcastle

  • Norfolk and Norwich University Hospital

    Norwich

  • Nottingham City Hospital

    Nottingham

  • Royal Oldham Hospital

    Oldham

  • Churchill Hospital

    Oxford

  • Derriford Hospital

    Plymouth

  • Queen Alexandra Hospital

    Portsmouth

  • Queen's Hospital

    Romford

  • Southampton General Hospital

    Southampton

  • Royal Stoke University Hospital

    Stoke-on-Trent

  • Singleton Hospital

    Swansea

  • Torbay Hospital

    Torquay

  • Royal Cornwall Hospital

    Truro

  • Worthing and St Richards Hospitals

    Worthing

Other trials in United Kingdom

About this study

Official title: A Randomised Phase II Evaluation of Molecular Guided Therapy for Diffuse Large B-Cell Lymphoma With Acalabrutinib

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.

Read more

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.

Read the detailed description

Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin's lymphomas. Whilst the majority of patients will respond well to conventional treatment (R-CHOP - rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), a significant number of patients lymphoma will not respond to initial therapy or their disease will return after completion of therapy. In a number of B-cell diseases an enzyme called, Bruton tyrosine kinase (BTK) prevents death of tumour cells, including in DLBCL. Acalabrutinib is an orally active BTK-inhibitor and it is thought that stopping BTK being activated may help in treating B-cell diseases. It is hypothesised that the addition of Acalabrutinib to standard R-CHOP immunochemotherapy may improve outcomes of patients with DLBCL.

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.

Being tested
R-CHOP, R-CHOP + acalabrutinib
Keywords
Lymphoma, Acalabrutinib, R-CHOP, DLBCL, Non Hodgkin Lymphoma, Haematological cancer, Bruton Tyrosine Kinase, Molecular Profiling, Chemoimmunotherapy
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • R-CHOPDrug

    Also called Rituximab, Cyclophosphamide, Doxorubicin, Vincristine

    Arm A patients will receive R-CHOP alone.

  • R-CHOP + acalabrutinibDrug

    Also called Rituximab, Cyclophosphamide, Doxorubicin, Vincristine

    Arm B patients will receive R-CHOP in combination with acalabrutinib.

Study groups in NCT04546620
Study groupRoleWhat they receive
Arm A ControlActive comparator6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy every 21 days.
Receives: Drug: R-CHOP
Arm B ExperimentalExperimental1 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.
Receives: Drug: R-CHOP + acalabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. To compare PFS between molecular groups.

    PFS interaction with cell of origin phenotype (ABC, GCB and unclassifiable).

    Measured: Last patient's last follow-up, approximately 4.5 years.

  2. To compare PFS between treatment groups.

    PFS interaction with clinical variables, including for example IPI, bulk, components of IPI, age and others to be determined in the SAP.

    Measured: Last patient's last follow-up, approximately 4.5 years.

  3. To compare overall survival (OS) between both treatment and molecular groups.

    Overall survival (OS), defined as time from registration to death from any cause.

    Measured: 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.

  4. To compare event free survival (EFS) between both treatment and molecular groups.

    Event-free survival (EFS), or time to treatment failure, defined as time from registration to any treatment failure including disease progression, or discontinuation of treatment for any reason.

    Measured: 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.

  5. To compare disease free survival (DFS) between both treatment and molecular groups.

    Disease-free survival (DFS), defined as time of documentation of disease-free state to disease recurrence or death as a result of lymphoma or acute toxicity of treatment.

    Measured: 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.

  6. To compare time to progression (TTP) between both treatment and molecular groups.

    Time to progression (TTP), defined as time from registration until documented lymphoma progression or death as a result of lymphoma. Deaths from other causes are censored at the time of death.

    Measured: Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a TTP event will be censored at the date of last follow-up.

  7. To compare duration of response (DoR) between both treatment and molecular groups.

    Response duration (DoR), defined as the time from documentation of response until the documentation of relapse or progression.

    Measured: Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a RD event will be censored at the date of last follow-up.

  8. To compare overall response rate (ORR) and complete response rate (CR) between both treatment groups.

    Assessment using the Lugano Response Criteria for Malignant Lymphoma.

    Measured: Complete and overall response rates, as recorded at the end of treatment (up to 21 weeks) .

  9. To assess differences in toxicity between assigned treatments.

    Evaluation of toxicity according to CTCAE version 5.

    Measured: At all visits up to 24 months follow-up.

  10. To assess differences in quality of life between treatment arms.

    Application of the EORTC QLQ-C30 and FACT-Lym questionnaires.

    Measured: At baseline, cycle 2 day 1, cycle 3 day 1, cycle 5 day 1, end of treatment and at 3, 6, 12, 20 and 24 month follow-ups. Each cycle is 21 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2020
  2. Study start19 Oct 2021
  3. Primary completionNov 2027 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
453 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04546620
Sponsor's protocol ID
RHM CAN1500
Acronym
REMoDL-A
Status last verified
Apr 2026
First submitted
11 Aug 2020
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing R-CHOP and R-CHOP + acalabrutinib in people with Diffuse Large B Cell Lymphoma, run by University Hospital Southampton NHS Foundation Trust at 33 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04546620.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in