Mantle Cell LymphomaPhase 2CARAMELNCT05004064
Acalabrutinib and Rituximab in Previously Untreated Mantle Cell Lymphoma
A Phase 2 study testing Acalabrutinib and Rituximab in people with Mantle Cell Lymphoma, run by University College, London at 12 sites in United Kingdom.
Trial summary
This is a phase II, single-arm, open-label, multicentre study of acalabrutinib and rituximab for elderly or frail patients with previously untreated mantle cell lymphoma. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Acalabrutinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 12 sitesUnited Kingdom
- Study dates
- 30 Nov 2023to 8 Jun 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥ 60 years of age.
- Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
- Stage II-IV MCL and requiring treatment in the opinion of the treating clinician.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- One or more of the following:
- Age 80 years or more
Show all 17Show fewer
- Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score 6 or greater
- Left ventricular ejection fraction (LVEF) less than or equal to 50% as assessed by echocardiogram
- Significant co-morbidities or cardiac risk factors making anthracycline-containing chemotherapy inadvisable
- Heart failure clinically determined by the presence of New York Heart Association (NYHA) failure grade II due to a cause other than MCL
- Impaired respiratory function with DLCO and/or FVC/FEV1 ratio less than 75% of predicted due to a cause other than MCL
- Significant respiratory illness e.g. moderate chronic obstructive pulmonary disease (COPD) bronchiectasis
- Other co-morbidities that in the Investigator's opinion which would preclude the use of standard full dose immuno-chemotherapy (to be discussed on a case-by-case basis with the TMG, via UCL CTC)
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules/tablets without difficulty.
- Negative serum or urine pregnancy test for women of childbearing potential (WOCBP).
- Willing to comply with the contraceptive requirements of the trial.
- Written informed consent.
Who cannot join
- Any prior therapy (including targeted inhibitors) for MCL (other than prior localised radiotherapy, a 10-day pulse of high dose steroids or continuous prednisolone above 20mg od or equivalent for symptom control).
- Patients considered by the investigator fit enough to receive standard, full dose cytotoxic immunochemotherapy as treatment for non-transplant eligible MCL e.g., full dose R-CHOP, VR-CAP, R-Bendamustine, R-FC.
- Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localised prostate cancer or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 5 years.
- Clinically significant cardiovascular disease such as uncontrolled arrhythmias, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification (33), or corrected QT interval (QTc) > 480 msec at screening.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Known history of infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral or fungal).
Show all 25Show fewer
- Known history of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components).
- Active bleeding or history of bleeding diathesis (e.g. haemophilia or von Willebrand disease).
- Uncontrolled AIHA (autoimmune haemolytic anaemia) or ITP (idiopathic thrombocytopenic purpura).
- Known presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days prior to the first dose of study drug.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) > 2 x upper limit of normal (ULN).
- Requires treatment with proton pump inhibitors (e.g. omeprazole, esomeprazole, lansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment to this study.
- History of significant cerebrovascular disease/event, including stroke or intracranial haemorrhage, within 6 months before the first dose of study drug.
- Major surgical procedure within 28 days prior to the first dose of study drug. Note: 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 study drug.
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HB core) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) test. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Those who are hepatitis C antibody or PCR positive will be excluded (those who are hepatitis C antibody positive but PCR negative will not be excluded). Note, if a patient with known HBV or HCV infection who is on current antiviral treatment meets serology criteria for trial eligibility then the case must be discussed with the TMG prior to registering the patient.
- Absolute neutrophil count <1.0 x 109/L (or requires growth factor support to maintain absolute neutrophil count >1.0 x 109/L) and/or platelets <75 x109/L unless related to bone marrow infiltration or splenomegaly due to underlying MCL (where platelets between 50-75 x109/L are acceptable)
- Total bilirubin > 1.5 x ULN, unless due to Gilbert's syndrome or of non-hepatic origin.
- AST and/or ALT > 3 x ULN.
- Calculated creatinine clearance <30 mL/min.
- History of or ongoing confirmed central nervous system (CNS) involvement
- Breastfeeding or pregnant.
- Concurrent participation in another therapeutic clinical trial.
- Live vaccine within 28 days prior to the first study drug dose
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United Kingdom12 sites
The Royal Bournemouth Hospital
Bournemouth
University Hospital of Wales
Cardiff
Beatson West of Scotland Cancer Centre
Glasgow
St. Bartholomew's Hospital
London
University College London Hospital
London
The Christie Hospital
Manchester
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral
Norfolk and Norwich University Hospital
Norwich
Cancer and Haematology Centre, Churchill Hospital
Oxford
Derriford Hospital
Plymouth
Royal Stoke Hospital
Stoke-on-Trent
Royal Cornwall Hospital
Truro
About this study
Official title: Phase II Study of Acalabrutinib and Rituximab for Elderly or Frail Patients With Previously Untreated Mantle Cell Lymphoma
This is a phase II, single-arm, open-label, multicentre study of acalabrutinib and rituximab for elderly or frail patients with previously untreated mantle cell lymphoma.
Read the detailed description
This is a Phase II, multicentre, single arm, open label pilot study to assess the safety and efficacy of acalabrutinib in combination with rituximab for previously untreated elderly frail mantle cell lymphoma patients.
48 patients will be recruited from 12 UK centres over 30 months.
Patients will receive acalabrutinib and rituximab for up to six cycles. The cycle length is 28 days. Specifically, patients will receive acalabrutinib, orally, at a dose of 100 mg twice daily for 28 days and rituximab 375 mg/m2 intravenously on day 1 (+/-3) of each cycle.* Patients with any degree of response at the Week 12 (end of cycle 3) and Week 24 assessments (end of cycle 6) will continue with acalabrutinib monotherapy at a dose of 100 mg twice daily until disease progression, the development of unacceptable toxicity or any other reason (whichever occurs sooner).
- Note: Acalabrutinib may be administered at a dose of 100 mg od po for cycle 1 day 1-7 at the local investigator's discretion. The dose should be escalated to full dose (100 mg bd) by day 8, cycle 1 if no toxicity is seen (see dose modification section). If a patient experiences toxicity during cycle 1 day 1-7 100 mg od po, the case must be discussed with the TMG to decide if acalabrutinib should continue. The CTC CARAMEL team should be contacted as soon as possible to arrange discussions with the TMG. Rituximab may be administered subcutaneously at a flat dose of 1400 mg from cycle 2 onwards following an intravenous dose of 375 mg/m2 in cycle 1. Consider splitting the first dose of rituximab at cycle 1 in the minority of MCL patients presenting with a white cell count of >25 x 109/L. Consider splitting 25-50 mg/m2 on D1 and 325-350 mg/m2 on D2 of cycle 1 (to a total of 375 mg/m2 over D1/D2) according to investigator and site preference. Full dose 375 mg/m2 IV (or s/c equivalent) should be given in all patients from cycle 2 as a single dose.
All patients will be followed up for a minimum of 2 years following being registered into the trial. For patients that have been in follow-up for more than 2 years, annual survival and disease status follow-up will continue until the end of the trial.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Acalabrutinib, Rituximab
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Patients will receive acalabrutinib 100mg twice daily for up to six 28 day cycles. Patients can receive 100mg once daily for cycle 1, day 1 to day 7, according to the investigator's discretion.
RituximabDrug
Patient will receive rituximab 375 mg/m2 IV on day 1 (+/- 3 days) of each cycle, for a maximum of 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib and rituximab | Experimental | Patients with untreated mantle cell lymphoma will receive acalabrutinib and rituximab for up to six cycles. Each cycle will comprise of acalabrutinib 100mg twice daily orally for 28 days and rituximab 375mg/m2 IV on day 1 (+/1 3 days) of every cycle. Receives: Drug: Acalabrutinib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
To determine the efficacy of acalabrutinib in combination with rituximab in terms of disease response.
Measured: 24 weeks
Secondary outcomes (4)
Progression free survival
Progression free survival measured from the date of first dose of acalabrutinib until the date of first documented progression or date of death from any cause.
Measured: From the date of first dose of acalabrutinib until the date of progression or death. Assessed up to 42 months.
Overall survival
Overall survival measured from the date of first dose of acalabrutinib until the date of death from any cause.
Measured: From the date of first dose of acalabrutinib until the date of death. Assessed up to 42 months.
Quality of life up to 24 months
The EORTC QLQ-C30 will be used to measure participant-assessed quality of life
Measured: At baseline, week 12, week 24, month 12 and month 24
Incidence and frequency of grade 1-2 and 3+ adverse events seen in both treatment arms.
Safety and toxicity will be characterised in terms of adverse events as assessed by CTCAE v5.0. The incidence and frequency of adverse events during treatment and after treatment will be assessed.
Measured: Between the start of study treatment and 30 calendar days post last IMP administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start30 Nov 2023
- Primary completion8 Jun 2026 (estimated)
- Study completion8 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Toby Eyre, Principal investigator, Churchill Hospital, Oxford, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004064
- Sponsor's protocol ID
- UCL/137775
- Other IDs
- 2021-002393-42
- Acronym
- CARAMEL
- Status last verified
- Mar 2026
- First submitted
- 8 Jun 2021
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Acalabrutinib and Rituximab for Elderly or Frail Patients With Previously Untreated Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT05004064
- Acronym / sponsor ID
- CARAMEL / UCL/137775
- Conditions
- Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 30 Nov 2023 (actual)
- Primary completion
- 8 Jun 2026 (estimated)
- Study completion
- 8 Jun 2028 (estimated)
- First posted
- 13 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II, single-arm, open-label, multicentre study of acalabrutinib and rituximab for elderly or frail patients with previously untreated mantle cell lymphoma.
Detailed description
This is a Phase II, multicentre, single arm, open label pilot study to assess the safety and efficacy of acalabrutinib in combination with rituximab for previously untreated elderly frail mantle cell lymphoma patients.
48 patients will be recruited from 12 UK centres over 30 months.
Patients will receive acalabrutinib and rituximab for up to six cycles. The cycle length is 28 days. Specifically, patients will receive acalabrutinib, orally, at a dose of 100 mg twice daily for 28 days and rituximab 375 mg/m2 intravenously on day 1 (+/-3) of each cycle.* Patients with any degree of response at the Week 12 (end of cycle 3) and Week 24 assessments (end of cycle 6) will continue with acalabrutinib monotherapy at a dose of 100 mg twice daily until disease progression, the development of unacceptable toxicity or any other reason (whichever occurs sooner).
- Note: Acalabrutinib may be administered at a dose of 100 mg od po for cycle 1 day 1-7 at the local investigator's discretion. The dose should be escalated to full dose (100 mg bd) by day 8, cycle 1 if no toxicity is seen (see dose modification section). If a patient experiences toxicity during cycle 1 day 1-7 100 mg od po, the case must be discussed with the TMG to decide if acalabrutinib should continue. The CTC CARAMEL team should be contacted as soon as possible to arrange discussions with the TMG. Rituximab may be administered subcutaneously at a flat dose of 1400 mg from cycle 2 onwards following an intravenous dose of 375 mg/m2 in cycle 1. Consider splitting the first dose of rituximab at cycle 1 in the minority of MCL patients presenting with a white cell count of >25 x 109/L. Consider splitting 25-50 mg/m2 on D1 and 325-350 mg/m2 on D2 of cycle 1 (to a total of 375 mg/m2 over D1/D2) according to investigator and site preference. Full dose 375 mg/m2 IV (or s/c equivalent) should be given in all patients from cycle 2 as a single dose.
All patients will be followed up for a minimum of 2 years following being registered into the trial. For patients that have been in follow-up for more than 2 years, annual survival and disease status follow-up will continue until the end of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib and rituximab | Experimental | Drug: Acalabrutinib, Drug: RituximabPatients with untreated mantle cell lymphoma will receive acalabrutinib and rituximab for up to six cycles. Each cycle will comprise of acalabrutinib 100mg twice daily orally for 28 days and rituximab 375mg/m2 IV on day 1 (+/1 3 days) of every cycle. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Men and women ≥ 60 years of age.
- Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
- Stage II-IV MCL and requiring treatment in the opinion of the treating clinician.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- One or more of the following:
Key exclusion criteria (25 listed)
- Any prior therapy (including targeted inhibitors) for MCL (other than prior localised radiotherapy, a 10-day pulse of high dose steroids or continuous prednisolone above 20mg od or equivalent for symptom control).
- Patients considered by the investigator fit enough to receive standard, full dose cytotoxic immunochemotherapy as treatment for non-transplant eligible MCL e.g., full dose R-CHOP, VR-CAP, R-Bendamustine, R-FC.
- Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localised prostate cancer or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 5 years.
- Clinically significant cardiovascular disease such as uncontrolled arrhythmias, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification (33), or corrected QT interval (QTc) > 480 msec at screening.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibPatients will receive acalabrutinib 100mg twice daily for up to six 28 day cycles. Patients can receive 100mg once daily for cycle 1, day 1 to day 7, according to the investigator's discretion. | Drug | Acalabrutinib and rituximab |
| RituximabPatient will receive rituximab 375 mg/m2 IV on day 1 (+/- 3 days) of each cycle, for a maximum of 6 cycles | Drug | Acalabrutinib and rituximab |
Primary outcome
Overall response rate
Time frame: 24 weeks
To determine the efficacy of acalabrutinib in combination with rituximab in terms of disease response.
4 secondary outcomes
Progression free survival
Time frame: From the date of first dose of acalabrutinib until the date of progression or death. Assessed up to 42 months.
Overall survival
Time frame: From the date of first dose of acalabrutinib until the date of death. Assessed up to 42 months.
Quality of life up to 24 months
Time frame: At baseline, week 12, week 24, month 12 and month 24
Incidence and frequency of grade 1-2 and 3+ adverse events seen in both treatment arms.
Time frame: Between the start of study treatment and 30 calendar days post last IMP administration.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toby Eyre principal investigator
Churchill Hospital, Oxford, United Kingdom
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib and Rituximab in people with Mantle Cell Lymphoma, run by University College, London at 12 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 17 inclusion and 25 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 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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?
Overall response rate (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jun 2026.