Comparing two treatments for untreated Splenic Marginal Zone Lymphoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Medical University of Vienna
  Vienna, Austria Recruiting
• Institut Bergonié
  Bordeaux, France Recruiting
• CHU de Grenoble
  Grenoble, France Recruiting
• Hôpital Saint Louis
  Paris, France Recruiting
• Hôpital Lyon-Sud
  Pierre-Bénite, France Recruiting
• CHRU Nancy Brabois
  Vandœuvre-lès-Nancy, France Recruiting

+5 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Emanuele Zucca, MD
• Email: ielsg@ior.usi.ch
• Phone: +41 58 666

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Polatuzumab vedotin with Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in untreated DLBCL (MCD/BN2/N1)

  This study tests a targeted combination therapy to see if it can treat previously untreated DLBCL with specific molecular subtypes.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07608978

• Nemtabrutinib plus rituximab for marginal zone lymphoma

  This phase 2 trial tests whether combining nemtabrutinib with rituximab can help people with marginal zone lymphoma.

  Recruiting Phase 2 City of Hope Medical Center · Duarte, California · NCT07583810

• Zanubrutinib, rituximab, lenalidomide plus tislelizumab for relapsed/refractory follicular lymphoma

  This trial tests whether adding the PD‑1 blocker tislelizumab to zanubrutinib, rituximab, and lenalidomide helps adults with relapsed or refractory follicular lymphoma who have had at least two prior therapies.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07418190

• Zanubrutinib plus rituximab for secondary HLH linked to B‑cell lymphoma

  This test tries zanubrutinib together with rituximab (plus short steroids and ruxolitinib, with emapalumab if needed) to treat people who have secondary HLH caused by B‑cell lymphoma.

  Recruiting Phase 4 The First Affiliated Hospital of Soochow University · Suzhou, Jiangsu · NCT07270835

• Zanubrutinib plus rituximab as first-line treatment for marginal zone lymphoma

  This tests whether combining zanubrutinib and rituximab is effective and safe as first-line treatment for people with CD20-positive marginal zone lymphoma who have not received prior systemic therapy.

  Recruiting Henan Cancer Hospital · Zhengzhou, Henan · NCT07233720

• ZR-MTX combo for newly diagnosed primary intraocular lymphoma

  This trial tests a Rituximab, Zanubrutinib, and methotrexate cocktail plus intravitreal methotrexate in people newly diagnosed with primary intraocular lymphoma to see if it can extend the time before the disease progresses.

  Recruiting Phase 2 Peking Union Medical College Hospital · Beijing, Beijing Municipality · NCT06973811

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.