Mantle Cell LymphomaPhase 2ZEBRANCT05635162
Zanubrutinib Plus Rituximab for Patients With Indolent Mantle Cell Lymphoma
A Phase 2 study testing Zanubrutinib and Rituximab in people with Mantle Cell Lymphoma, run by University College, London at 13 sites in United Kingdom.
Trial summary
Phase II, multicentre, randomised, open-label study to assess the benefit of early intervention with fixed duration, time-limited zanubrutinib-rituximab in indolent mantle cell lymphoma (MCL) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Zanubrutinib 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
- 50 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- 17 May 2024to Oct 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or over.
- Life expectancy ≥ 6 months.
- Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, D2 or D3.
- Stage II-IV MCL measurable by CT imaging or by white cell count (WCC)/BM infiltration.
- 'Indolent' MCL, defined as 1 or more of the following:
- Observation with no treatment for a minimum of 6 months after the initial diagnosis
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- Leukaemic non-nodal variant (lymphocytosis/splenomegaly only without nodal involvement)
- Low tumour volume (largest lymph node ≤ 3cm in maximal diameter), proliferation fraction (Ki67 or equivalent) ≤30% and classical morphology (non-blastoid/pleomorphic)
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
- Absolute neutrophil count ≥1.0 x 109/L and platelets ≥75 x 109/L independent of growth factor support.
- AST and/or ALT ≤3 x upper limit of normal (ULN).
- Total Bilirubin ≤1.5 x ULN unless due to Gilberts syndrome or of non-hepatic origin unless directly attributable to the patient's MCL.
- Calculated creatinine clearance ≥30 mL/min. Glomerular filtration rate (GFR) ≥30 mL/min directly measured with 24 hour urine collection, or creatinine clearance calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight)/ (72 x creatinine), for women x 0, 85).
- Able to give voluntary written informed consent.
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
- Negative serum or urine pregnancy test for women of childbearing potential (WOCBP).
- Willing to comply with the contraceptive requirements of the trial.
Who cannot join
- Any prior therapy for MCL, including prior radiotherapy.
- Central nervous system (CNS) involvement of MCL.
- Uncontrolled infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral or fungal). Patients with well-controlled HIV status (undetectable viral load) will not be excluded.
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HB core) positive and who are surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) test. Those who are hepatitis B HbsAg positive or hepatitis B PCR positive will be excluded. Those who are hepatitis C antibody and PCR positive will be excluded (those who are hepatitis C antibody positive and PCR negative will not be excluded).
- No progression requiring treatment since initial diagnosis.
- Vaccinated with live vaccines (not including messenger ribonucleic acid (mRNA), viral vector or other non-live COVID19 vaccines) within four weeks prior to randomisation.
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- Major surgical procedure within 28 days prior to randomisation. 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.
- 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.
- Requirement for moderate or strong CYP3A inducers. Moderate and strong CYP3A inhibitors are allowed although these should be switched to agents causing less CYP3A inhibition where possible.
- Requirement for vitamin K antagonists (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed about the potential risk of bleeding alongside zanubrutinib). Requires ongoing treatment with warfarin or warfarin derivatives
- Active bleeding or history of bleeding diathesis (e.g. haemophilia or von Willebrand disease) or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
- Clinically significant cardiovascular disease such as uncontrolled arrhythmias, or history of ventricular tachycardia, ventricular fibrillation, torsades de points or myocardial infarction within 6 months of randomisation, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification, or corrected QT interval (QTc) > 480 msec, second-degree atrioventricular block Type II, third-degree atrioventricular block at randomisation, unstable angina within 3 months prior to randomisation.
- History of stroke or intracranial haemorrhage within 6 months prior to randomisation.
- Any other severe medical or psychiatric illness that in the opinion of the investigator would interfere with participation in this clinical study.
- Malabsorption syndrome, unable to swallow capsules, 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.
- Women who are pregnant or breastfeeding.
- Male participants with female partners of childbearing potential who are unwilling to use appropriate contraception methods.
- Concurrent treatment with another investigational agent.
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
- Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
- Severe or debilitating pulmonary disease.
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs
- Concurrent participation in another therapeutic clinical trial.
- Active and/or ongoing autoimmune anaemia and/or autoimmune thrombocytopenia (eg. idiopathic thrombocytopenia purpura).
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United Kingdom13 sites, 13 recruiting
- Recruiting
Royal Derby Hospital
Derby
Meghna Ruparelia
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow
Matt Wilson
- Recruiting
Clatterbridge Cancer Centre
Liverpool
Matt Wells
- Recruiting
Guy's Hospital
London
Suzanne Arulogun
- Recruiting
St Bartholomew's Hospital
London
Rebecca Auer
- Recruiting
University College London Hospital
London
Maria Marzolini
- Recruiting
Christie Hospital
Manchester
Kim Linton
- Recruiting
Norfolk and Norwich University Hospitl
Norwich
Joel Cunningham
- Recruiting
Nottingham City Hospital
Nottingham
Mark Bishton
- Recruiting
Churchill Hospital
Oxford
Toby Eyre
- Recruiting
Derriford Hospital
Plymouth
David Lewis
- Recruiting
Southampton General Hospital
Southampton
David Dutton
- Recruiting
Royal Cornwall Hospital
Truro
Michelle Furtado
About this study
Official title: Zanubrutinib Plus Rituximab (Zanu -R) as Fixed Duration, Early Intervention Versus Observation for Patients With Indolent Mantle Cell Lymphoma: a Randomised Phase II Clinical Trial
Phase II, multicentre, randomised, open-label study to assess the benefit of early intervention with fixed duration, time-limited zanubrutinib-rituximab in indolent mantle cell lymphoma (MCL)
Read the detailed description
This is a phase II, multicentre, randomised open label study to assess the safety and efficacy of zanubrutinib in combination with rituximab for previously untreated indolent MCL patients.
50 patients will be recruited from 15 UK centres over 30 months.
Enrolled patients will be randomised (1:1) to ongoing observation (control arm; arm A) or fixed-duration zanubrutinib-rituximab (experimental arm; arm B). Patients will discontinue zanubrutinib-rituximab after 6 cycles of therapy or sooner in the advent of unacceptable toxicity or any other reason.
All patients will be followed up for a minimum of 2 years after randomisation. Patients in arm B who develop disease progression and require further therapy after the initial time-limited Zanu-R will receive standard of care therapy according to front line treatment available at that time.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Zanubrutinib, 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.
ZanubrutinibDrug
Zanubrutinib dose is 160 mg twice daily (BD) orally (PO) on days 1-28 of each 28-day cycle.
RituximabDrug
Rituximab 375 mg/m2 intravenous (IV)* on day 1 (+/-3 days) of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Control | No intervention | Active observation |
| Arm B: Experimental | Experimental | Time limited Zanubrutinib-R 6 x 28 day cycles Receives: Drug: Zanubrutinib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival
To determine the effect of fixed-duration Zanu-R on Event-free survival (EFS) compared to active observation
Measured: From date of randomisation until whichever comes first: occurrence of active disease, new MCL treatment or death (any cause) up to 60 months
Secondary outcomes (7)
Progression free survival
To determine the effect of fixed-duration Zanu-R on Progression free survival (PFS) compared to active observation
Measured: Randomisation until disease progression up to 60 months
Overall survival
To determine the effect of fixed-duration Zanu-R on overall survival (OS) compared to active observation
Measured: Randomisation until date of death up to 60 months
Time to next treatment
To determine the effect of fixed-duration Zanu-R on time to next treatment (TTNT) compared to active observation
Measured: Randomisation until date of initiation of subsequent treatment up to 60 months
Time to second progression
To determine the effect of fixed-duration Zanu-R on time to second progression compared to active observation
Measured: From date of randomisation or date of first progression until date of second progression or death from any cause up to 60 months
Overall response rate to Zanu-R
To determine the effect of fixed-duration Zanu-R on overall response rate (ORR) at the end of 6 cycles of treatment
Measured: From start of treatment until 24 weeks post administration of Zanu-R
Overall response rate to re-treatment with covalent BTKi
To determine the ORR to re-treatment with covalent BTKi in experimental arm
Measured: From the start of further treatment with a BTKi through to study completion, an average of 60 months
Safety and Toxicity
To assess the worst grade of each adverse event for each patient. Grades 1-2 and grades 3-5 will be compared between the arms
Measured: From informed consent until 28 weeks post randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2022
- Study start17 May 2024
- Primary completionOct 2028 (estimated)
- Study completionOct 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05635162
- Sponsor's protocol ID
- UCL 146660
- Acronym
- ZEBRA
- Status last verified
- Apr 2025
- First submitted
- 31 Oct 2022
- Last updated
- 16 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zanubrutinib Plus Rituximab (Zanu -R) as Fixed Duration, Early Intervention Versus Observation for Patients With Indolent Mantle Cell Lymphoma: a Randomised Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT05635162
- Acronym / sponsor ID
- ZEBRA / UCL 146660
- Conditions
- Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- BeiGene
- Study start
- 17 May 2024 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 2 Dec 2022 (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.
Phase II, multicentre, randomised, open-label study to assess the benefit of early intervention with fixed duration, time-limited zanubrutinib-rituximab in indolent mantle cell lymphoma (MCL)
Detailed description
This is a phase II, multicentre, randomised open label study to assess the safety and efficacy of zanubrutinib in combination with rituximab for previously untreated indolent MCL patients.
50 patients will be recruited from 15 UK centres over 30 months.
Enrolled patients will be randomised (1:1) to ongoing observation (control arm; arm A) or fixed-duration zanubrutinib-rituximab (experimental arm; arm B). Patients will discontinue zanubrutinib-rituximab after 6 cycles of therapy or sooner in the advent of unacceptable toxicity or any other reason.
All patients will be followed up for a minimum of 2 years after randomisation. Patients in arm B who develop disease progression and require further therapy after the initial time-limited Zanu-R will receive standard of care therapy according to front line treatment available at that time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomised
| Arm | Type | Receives |
|---|---|---|
| Arm A: Control | No intervention | –Active observation |
| Arm B: Experimental | Experimental | Drug: Zanubrutinib, Drug: RituximabTime limited Zanubrutinib-R 6 x 28 day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 18 years of age or over.
- Life expectancy ≥ 6 months.
- Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, D2 or D3.
- Stage II-IV MCL measurable by CT imaging or by white cell count (WCC)/BM infiltration.
- 'Indolent' MCL, defined as 1 or more of the following:
Key exclusion criteria (24 listed)
- Any prior therapy for MCL, including prior radiotherapy.
- Central nervous system (CNS) involvement of MCL.
- Uncontrolled infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral or fungal). Patients with well-controlled HIV status (undetectable viral load) will not be excluded.
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HB core) positive and who are surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) test. Those who are hepatitis B HbsAg positive or hepatitis B PCR positive will be excluded. Those who are hepatitis C antibody and PCR positive will be excluded (those who are hepatitis C antibody positive and PCR negative will not be excluded).
- No progression requiring treatment since initial diagnosis.
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 |
|---|---|---|
| ZanubrutinibZanubrutinib dose is 160 mg twice daily (BD) orally (PO) on days 1-28 of each 28-day cycle. | Drug | Arm B: Experimental |
| RituximabRituximab 375 mg/m2 intravenous (IV)* on day 1 (+/-3 days) of each 28-day cycle | Drug | Arm B: Experimental |
Primary outcome
Event free survival
Time frame: From date of randomisation until whichever comes first: occurrence of active disease, new MCL treatment or death (any cause) up to 60 months
To determine the effect of fixed-duration Zanu-R on Event-free survival (EFS) compared to active observation
7 secondary outcomes
Progression free survival
Time frame: Randomisation until disease progression up to 60 months
Overall survival
Time frame: Randomisation until date of death up to 60 months
Time to next treatment
Time frame: Randomisation until date of initiation of subsequent treatment up to 60 months
Time to second progression
Time frame: From date of randomisation or date of first progression until date of second progression or death from any cause up to 60 months
Overall response rate to Zanu-R
Time frame: From start of treatment until 24 weeks post administration of Zanu-R
Overall response rate to re-treatment with covalent BTKi
Time frame: From the start of further treatment with a BTKi through to study completion, an average of 60 months
Safety and Toxicity
Time frame: From informed consent until 28 weeks post randomisation
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 16 Apr 2025.
- Individual participant dataSharing planned: Undecided
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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.
13 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 Zanubrutinib and Rituximab in people with Mantle Cell Lymphoma, run by University College, London at 13 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 24 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: looking for participants now, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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?
Contact ZEBRA Trial Manager ((+44) (0)2076799860, ctc.zebra@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (time frame: From date of randomisation until whichever comes first: occurrence of active disease, new MCL treatment or death (any cause) up to 60 months). 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 16 Apr 2025.