Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment

A Multicenter, Open-label, Randomized Controlled Study of Orelabrutinib in Combination With Bendamustine and Rituximab Versus Bendamustine and Rituximab in the Treatment of Transplant-Ineligible, Intermediate- to High-Risk Mantle Cell Lymphoma (MCL)

This multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of Orelabrutinib in combination with Bendamustine and Rituximab (OBR) versus Bendamustine and Rituximab (BR) in patients with intermediate- to high-risk mantle cell lymphoma (MCL) who are ineligible for transplantation. The primary objective is to assess the complete response (CR) rate during the induction phase, with secondary objectives including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Exploratory analysis will investigate the correlation between tumor biomarkers and treatment efficacy.

Inclusion Criteria:

• Diagnosed with MCL (mantle cell lymphoma) through flow cytometry or histopathology, and has not received prior treatment.
• Age > 18 years of age, both genders are eligible.
• Ann Arbor stage II-IV; for stage II subjects, those who require systemic therapy based on the investigator's judgment are eligible.
• At least one measurable lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Any one of the following high-risk factors is present: MIPI score of 4-11, Ki67 > 50%, TP53 abnormality, blastic or pleomorphic variation.
• Patients who are not suitable candidates for autologous hematopoietic stem cell transplantation.
• Laboratory tests (blood routine, liver and kidney function) meet the following requirements: a) Blood routine: White blood cell count ≥3.0×10^9/L, absolute neutrophil count ≥1.5×10^9/L, hemoglobin ≥90g/L, platelet count ≥75×10^9/L. b) Liver function: Transaminases ≤2.5 times the upper limit of normal, bilirubin ≤1.5 times the upper limit of normal. c) Serum creatinine 44-133 mmol/L.
• The investigator judges that the subject's life expectancy is greater than 12 weeks from the time of screening.
• Willing and able to participate in all required assessments and procedures of the study protocol.

Exclusion Criteria:

• Patients who have previously received treatment with BTK inhibitors.
• Patients with severe complications or serious infections.
• Patients with uncontrolled cardiovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc.
• Patients with active infections requiring systemic treatment, including bacterial, fungal, and viral infections.
• HIV-infected individuals.
• Patients with mental disorders or those who are known or suspected to be unable to fully comply with the study protocol.
• Patients whom the investigator judges to have other conditions that make them unsuitable for participation in this study.