Phase 3, Interventional, Multicentre, Open-label, Randomized Study Comparing Rituximab Plus Zanubrutinib to Rituximab Monotherapy in Previously Untreated, Symptomatic Splenic Marginal Zone Lymphoma (RITZ)
The goal of this clinical trial is to compare the efficacy and tolerability of the combination of two medicinal products, rituximab, and zanubrutinib, compared to rituximab monotherapy in patients with Splenic Marginal Zone Lymphoma (SMZL), previously untreated and who need systemic treatment. The main questions it aims to answer are: * Is the combination rituximab and zanubrutinib a more effective therapy than rituximab monotherapy? * Is the combination therapy, rituximab and zanubrutinib, well tolerated? Study participants will be put into one of the two treatment groups (rituximab and zanubrutinib or rituximab alone) for a maximum of two years and will undergo regular visits until three years from treatment start.
• 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