A Multicenter, Prospective Clinical Trial With a Concurrent Control Evaluating Methotrexate Combined With Rituximab,Sintilimab and Pirtobrutinib vs. Investigator-Selected Standard of Care in Treatment-Naive PCNSL

The goal of this clinical trial is to evaluate the efficacy and safety of a four-drug combination regimen as first-line treatment for adults aged 18 years and older with newly diagnosed primary central nervous system lymphoma (PCNSL). The main questions it aims to answer are: Does the combination of pirtobrutinib, sintilimab, rituximab, and high-dose methotrexate achieve a higher complete response rate than standard treatment for newly diagnosed PCNSL? What is the safety and tolerability profile of this four-drug combination regimen? Researchers will compare the experimental four-drug combination to investigator-selected standard-of-care regimens (all based on high-dose methotrexate) to see if the experimental regimen improves complete response rate, progression-free survival, and overall survival while maintaining an acceptable safety profile. Participants will: Be assigned to either the experimental group or the standard treatment group based on their personal preference Receive 6 cycles of induction therapy (21 days per cycle) with their assigned treatment regimen Undergo regular clinical assessments, including contrast-enhanced brain MRI scans, blood tests, and cerebrospinal fluid examinations Complete the EORTC QLQ-C30 quality-of-life questionnaire at baseline, mid-treatment, end of treatment, and follow-up visits Receive optional consolidation or maintenance therapy based on their response to induction treatment Be followed for up to 2 years after completing treatment to monitor for disease progression and long-term outcomes

NCT Number	NCT07350850
Lead Sponsor	Tongji Hospital Collaborators: Shanxi Provincial People's Hospital, First Affiliated Hospital of Fujian Medical University, The General Hospital of Western Theater Command, China-Japan Union Hospital, Jilin University
Conditions	PCNSL, Primary Central Nervous System Lymphoma
Enrollment	77 participants
Start Date	2025-12-25
Primary Completion	2028-12-31 (estimated)
Study Completion	2029-06-30 (estimated)
Updated on ClinicalTrials.gov	2026-06-02