Zanubrutinib Plus Rituximab for Patients With Indolent Mantle Cell Lymphoma
NCT ID: NCT05635162
Last Updated: 2025-04-16
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.
RECRUITING
PHASE2
50 participants
INTERVENTIONAL
2024-05-17
2028-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Zanubrutinib in the Treatment of Recurrent Refractory Mantle Cell Lymphoma
NCT05486013
Zanubrutinib-rituximab(ZR) in Patients With Newly Diagnosed Untreated Mantle Cell Lymphoma
NCT05504603
A Study of the Zanubrutinib Given in Combination With Bendamustine and Rituximab in (Elderly or TP53 Alterations or Chemotherapy Intolerance) Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT06136351
This is a Phase II, Open-label, Multicentre Study of Zanubrutinib-containing Regimens in Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT06427213
A Study to Investigate the Efficacy of Zanubrutinib Plus Rituximab Compared With Bendamustine Plus Rituximab in Adults With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation
NCT04002297
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
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
Active observation
No interventions assigned to this group
Arm B: Experimental
Time limited Zanubrutinib-R 6 x 28 day cycles
Zanubrutinib
Zanubrutinib dose is 160 mg twice daily (BD) orally (PO) on days 1-28 of each 28-day cycle.
Rituximab
Rituximab 375 mg/m2 intravenous (IV)\* on day 1 (+/-3 days) of each 28-day cycle
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Zanubrutinib
Zanubrutinib dose is 160 mg twice daily (BD) orally (PO) on days 1-28 of each 28-day cycle.
Rituximab
Rituximab 375 mg/m2 intravenous (IV)\* on day 1 (+/-3 days) of each 28-day cycle
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Life expectancy ≥ 6 months.
3. 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.
4. Stage II-IV MCL measurable by CT imaging or by white cell count (WCC)/BM infiltration.
5. 'Indolent' MCL, defined as 1 or more of the following:
* Observation with no treatment for a minimum of 6 months after the initial diagnosis
* 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)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
7. Absolute neutrophil count ≥1.0 x 109/L and platelets ≥75 x 109/L independent of growth factor support.
8. AST and/or ALT ≤3 x upper limit of normal (ULN).
9. Total Bilirubin ≤1.5 x ULN unless due to Gilberts syndrome or of non-hepatic origin unless directly attributable to the patient's MCL.
10. 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).
11. Able to give voluntary written informed consent.
12. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
13. Negative serum or urine pregnancy test for women of childbearing potential (WOCBP).
14. Willing to comply with the contraceptive requirements of the trial.
Exclusion Criteria
2. Central nervous system (CNS) involvement of MCL.
3. 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.
4. 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).
5. No progression requiring treatment since initial diagnosis.
6. Vaccinated with live vaccines (not including messenger ribonucleic acid (mRNA), viral vector or other non-live COVID19 vaccines) within four weeks prior to randomisation.
7. 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.
8. 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.
9. 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.
10. 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
11. 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.
12. 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.
13. History of stroke or intracranial haemorrhage within 6 months prior to randomisation.
14. Any other severe medical or psychiatric illness that in the opinion of the investigator would interfere with participation in this clinical study.
15. 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.
16. Women who are pregnant or breastfeeding.
17. Male participants with female partners of childbearing potential who are unwilling to use appropriate contraception methods.
18. Concurrent treatment with another investigational agent.
19. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
20. Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
21. Severe or debilitating pulmonary disease.
22. 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
23. Concurrent participation in another therapeutic clinical trial.
24. Active and/or ongoing autoimmune anaemia and/or autoimmune thrombocytopenia (eg. idiopathic thrombocytopenia purpura).
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
BeiGene
INDUSTRY
University College, London
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Royal Derby Hospital
Derby, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
Clatterbridge Cancer Centre
Liverpool, , United Kingdom
Guy's Hospital
London, , United Kingdom
St Bartholomew's Hospital
London, , United Kingdom
University College London Hospital
London, , United Kingdom
Christie Hospital
Manchester, , United Kingdom
Norfolk and Norwich University Hospitl
Norwich, , United Kingdom
Nottingham City Hospital
Nottingham, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Derriford Hospital
Plymouth, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Royal Cornwall Hospital
Truro, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Meghna Ruparelia
Role: primary
Matt Wilson
Role: primary
Matt Wells
Role: primary
Suzanne Arulogun
Role: primary
Rebecca Auer
Role: primary
Maria Marzolini
Role: primary
Kim Linton
Role: primary
Joel Cunningham
Role: primary
Mark Bishton
Role: primary
Toby Eyre
Role: primary
David Lewis
Role: primary
David Dutton
Role: primary
Michelle Furtado
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
UCL 146660
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.