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Combining Zanubrutinib and Rituximab for Indolent Mantle Cell Lymphoma

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 2 Interventional University College, London · NCT05635162

This study is testing if a new combination of two medications, zanubrutinib and rituximab, can help people with indolent mantle cell lymphoma who haven't been treated before.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment50 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity College, London Academic / other
Drugs / interventionszanubrutinib, rituximab
Locations13 sites (Derby and 12 other locations)
Trial IDNCT05635162 on ClinicalTrials.gov

What this trial studies

This phase II, multicentre, randomised open-label study evaluates the safety and efficacy of zanubrutinib in combination with rituximab for patients with previously untreated indolent mantle cell lymphoma (MCL). A total of 50 patients will be recruited from 15 centers across the UK and will be randomly assigned to either ongoing observation or a fixed-duration treatment with zanubrutinib-rituximab. The treatment will last for 6 cycles, after which patients will be monitored for at least 2 years to assess outcomes and any disease progression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and over with pathologically confirmed indolent mantle cell lymphoma and specific clinical characteristics.

Not a fit: Patients with aggressive forms of mantle cell lymphoma or those who have received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with indolent mantle cell lymphoma, potentially improving their outcomes.

How similar studies have performed: While this approach is being tested in this specific context, similar combinations of targeted therapies and monoclonal antibodies have shown promise in other studies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. 18 years of age or over.
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:

1. Any prior therapy for MCL, including prior radiotherapy.
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).

Where this trial is running

Derby and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Mantle Cell Lymphoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.