RecruitingPhase 2NCT07350850

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

In Treatment-Naive Patients With Primary Central Nervous System Lymphoma (PCNSL): A Multicenter, Prospective, Concurrent-Control Study of Methotrexate, , Rituximab,, Sintilimab ,Pirtobrutinib Versus Investigator-Selected Standard of Care

Sponsor

Tongji Hospital

Enrollment

77 participants

Start Date

Dec 25, 2025

Study Type

INTERVENTIONAL

Conditions

Primary Central Nervous System Lymphoma PCNSL

Summary

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

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new combination drug regimen — methotrexate, rituximab, sintilimab (an immunotherapy), and pirtobrutinib — for people newly diagnosed with primary central nervous system lymphoma (PCNSL), a rare type of lymphoma that only occurs in the brain or eyes. A separate comparison group receives standard physician-chosen treatment. **You may be eligible if...** - You are 18 or older - You have a confirmed diagnosis of primary CNS diffuse large B-cell lymphoma (brain or eye lymphoma) - You have not received any prior treatment for lymphoma (steroids are OK) - Your tumor is visible on brain MRI or you have lymphoma cells in the spinal fluid - You are in reasonable health (ECOG 0–3) with expected survival over 3 months **You may NOT be eligible if...** - You have previously received PD-1/PD-L1 immunotherapy - You have a serious uncontrolled heart condition, active serious infection, or active hepatitis B or C - You have HIV - You have an autoimmune disease requiring systemic treatment in the past 2 years - You have had an organ transplant or stem cell transplant - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGPirtobrutinib, Sintilimab, Rituximab, Methotrexate

Participants in this single-arm prospective cohort will receive the investigational combination therapy: Rituximab (375 mg/m\^2, IV, Day 0), Methotrexate (3.5 g/m\^2, IV, Day 1; adjusted to 1.0 g/m\^2 for elderly/frail patients), Sintilimab (200 mg, IV, Day 1), Pirtobrutinib (200 mg, PO, Days 1-21). Treatment cycles repeat every 21 days for up to 6 cycles.

DRUGStandard of Care (Investigator Selected)

Patients eligible for curative-intent therapy will receive one of the following three guideline-recommended, high-dose methotrexate (HD-MTX)-based first-line regimens, selected by the treating physician based on patient age, performance status, comorbidities, and clinical judgment: MATRix Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Cytarabine 2 g/m² IV twice daily on Days 2-3; Thiotepa 30 mg/m² orally on Day 4. Cycle length: 21 days, up to 6 cycles. RMT Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Temozolomide 150 mg/m² orally once daily on Days 1-5. Cycle length: 21 days, up to 6 cycles. MR-BTKi Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Covalent BTK inhibitor (Ibrutinib 560 mg qd, Zanubrutinib 160 mg bid, or Orelabrutinib 150 mg qd) orally on Days 1-21. Cycle length: 21 days, up to 6 cycles.