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Comparing two treatments for untreated Splenic Marginal Zone Lymphoma

Phase 3, Interventional, Multicentre, Open-label, Randomized Study Comparing Rituximab Plus Zanubrutinib to Rituximab Monotherapy in Previously Untreated, Symptomatic Splenic Marginal Zone Lymphoma (RITZ)

Phase 3 Interventional International Extranodal Lymphoma Study Group (IELSG) · NCT05735834

This study is testing whether a combination of two drugs, rituximab and zanubrutinib, works better than just rituximab alone for people with untreated Splenic Marginal Zone Lymphoma.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorInternational Extranodal Lymphoma Study Group (IELSG) Academic / other
Drugs / interventionsprednisone, rituximab, zanubrutinib
Locations55 sites (Vienna and 54 other locations)
Trial IDNCT05735834 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and tolerability of a combination therapy using rituximab and zanubrutinib compared to rituximab alone in patients with untreated Splenic Marginal Zone Lymphoma (SMZL). Participants will be randomly assigned to one of two treatment groups for a maximum of two years, followed by a three-year follow-up period. The study will assess progression-free survival and monitor any adverse effects associated with the treatments. Approximately 120 subjects will be enrolled in this multicenter, open-label Phase III trial.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of untreated Splenic Marginal Zone Lymphoma.

Not a fit: Patients with prior treatments for SMZL or those with certain genetic mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with untreated SMZL, potentially improving their progression-free survival.

How similar studies have performed: Other studies have shown promising results with combination therapies in similar conditions, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Ability to understand and willingness to sign a written informed consent in accordance with ICH/GCP regulations before registration and prior to any trial-specific procedures.
* Confirmed diagnosis of SMZL, including Matutes immunophenotype score \<3. Evaluation of the following features is desirable: absence of CD103 expression by flow cytometry, absence of Cyclin D1, BCL6, and CD10 expression by immunohistochemistry, and absence of the MYD88 L265P mutation. Patients with prominent splenomegaly and involvement of the splenic hilar and/or extra hilar lymph nodes are eligible
* Previously untreated disease. Patients with prior hepatitis C virus (HCV) infection who underwent HCV eradication and have persistent SMZL after 3 months post-eradication can be included.
* Treatment needs according to the ESMO guideline criteria
* Measurable lesions
* Age ≥ 18 years.
* European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, platelet count ≥ 50 x 109/L, Hb \> 7.5 g/dl. Values below such thresholds are allowed if attributable to the underlying lymphoma. Transfusions are allowed if clinically indicated during screening.
* Adequate hepatic and renal function and coagulation parameters
* Patient able and willing to swallow trial drugs as whole tablet/capsule

Exclusion Criteria:

* Previous splenectomy.
* Any systemic therapy for SMZL.
* Patients with central nervous system (CNS) involvement.
* Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
* Clinically significant cardiovascular disease
* History of cerebrovascular accident or intracranial hemorrhage within 6 months before registration and known bleeding disorders (eg, von Willebrand's disease or hemophilia).
* History of confirmed progressive multifocal leukoencephalopathy (PML).
* Concomitant diseases that require anticoagulant therapy with warfarin or phenprocoumon or other vitamin K antagonists and patients treated with dual anti-platelet therapy. Patients being treated with factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban), direct thrombin inhibitors (e. dabigatran) low molecular weight heparin (LMWH), or single anti-platelet agents (eg. aspirin, clopidogrel) can be included but must be properly informed about the potential risk of bleeding.
* Malabsorption syndrome or other condition that precludes the enteral route of administration.
* Any uncontrolled active systemic infection requiring intravenous antimicrobial treatment.
* Known human immunodeficiency virus (HIV) infection.
* Active COronaVIrus Disease 19 (COVID-19) infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic.
* Active chronic hepatitis C or hepatitis B virus infection
* Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune. thrombocytopenia) requiring steroid therapy with \> 20 mg daily of prednisone dose or equivalent.
* Known hypersensitivity to trial drugs or any component of the trial drugs.
* Concomitant treatment with strong CYP3A inducers or inhibitors
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and/or would make the patient inappropriate for enrolment into this trial.
* Pregnancy or breastfeeding.
* Concurrent participation in another therapeutic clinical trial.

Where this trial is running

Vienna and 54 other locations

+5 more sites — see ClinicalTrials.gov for the full list.

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 Splenic Marginal Zone 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.