Study of Zanubrutinib Combined With Pola-R-CHP or Rituximab and High-Dose MTX for Newly Diagnosed High-Risk Diffuse Large B-Cell Lymphoma

What this Trial Is About

Diffuse large B-cell lymphoma DLBCL is the most common type of non-Hodgkins lymphoma, with first-line treatment using R-CHOP curing only about 50% to 60% of patients. This research evaluates the BTK inhibitor zanubrutinib combined with Pola-R-CHP or zanubrutinib combined with rituximab and high-dose MTX in patients with DLBCL who have specific high-risk factors such as IPI score 2 or more, ABC subtype, double-expressor lymphoma, double-hit lymphoma, and involvement of special sites including the central nervous system. The study aims to improve outcomes for these high-risk patients by exploring new combination therapies. Participants receive zanubrutinib with the Pola-R-CHP regimen, which includes zanubrutinib 160mg twice daily days 1 to 21 of cycles 1 to 6 polatuzumab 1.8mgkg, rituximab 375mgm2, cyclophosphamide 750mgm2, doxorubicin 50mgm2 intravenously on day 1 of cycles 1 to 6 and prednisone 60mgm2 days 1 to 5 of each cycle. For those with primary central nervous system DLBCL, zanubrutinib is combined with rituximab and high-dose methotrexate. The treatment period covers six cycles. During the study, participants undergo regular assessments to measure the best complete remission rate within 24 weeks after treatment starts. Secondary outcomes include overall response rate, two-year progression-free survival, and overall survival rates. Safety and efficacy are monitored throughout, with evaluations based on clinical response and lab results. The total study duration includes follow-up for up to two years after treatment initiation for the last participant.

Application of Zanubrutinib-based Combination Regimens in the Treatment of Newly-diagnosed Diffuse Large B-cell Lymphoma