RecruitingPhase 2NCT07350850

A Multicenter Two-Cohort Study of Methotrexate, Rituximab, Sintilimab and Pirtobrutinib for Treatment-Naive PCNSL vs. Real-World Investigator-Selected Treatment (Observational Cohort)

In Treatment-Naive Patients With Primary Central Nervous System Lymphoma (PCNSL): A Multicenter Two-Cohort Study of Methotrexate Combined With Rituximab, Sintilimab and Pirtobrutinib (Prospective Interventional Cohort) vs. Real-World Investigator-Selected Treatment (Observational Cohort)

Sponsor

Tongji Hospital

Enrollment

110 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 a new combination therapy for patients with newly diagnosed Primary Central Nervous System Lymphoma (PCNSL). The main questions it aims to answer are: (1) Does the combination of Methotrexate, Rituximab, Sintilimab, and Pirtobrutinib improve the Complete Remission Rate (CRR)? (2) Is this regimen safe and tolerable for patients? Researchers will compare this interventional group to a real-world observational group (receiving standard investigator-selected treatments) to see if the new combination improves treatment response and survival.

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)

Participants in the Real-World Observational Cohort receive investigator-selected treatments based on clinical guidelines. 1.Specific regimens include: 1. MATRix: Methotrexate (3.5g/m², d1), Cytarabine (2g/m², d2-3), Rituximab (375mg/m², d0), and Thiotepa (30mg/m², d4) every 21 days . 2. RMT: Methotrexate (3.5g/m², d1), Rituximab (375mg/m², d0), and Temozolomide (150mg/m², d1-5) every 21 days . 3. MR-BTKi: Methotrexate (3.5g/m², d1), Rituximab (375mg/m², d0), and a covalent BTK inhibitor (Ibrutinib 560mg qd, Zanubrutinib 160mg bid, or Orelabrutinib 150mg qd) . 2.Palliative Care Subgroup: Radiotherapy, low-dose chemotherapy, or supportive care .Radiotherapy: Low-dose Whole Brain Radiotherapy (WBRT ≤ 30Gy). Low-dose Chemotherapy: Reduced-dose Methotrexate (e.g., 1.0g/m²) or other single-agent chemotherapy. Best Supportive Care: Management of symptoms and complications without intensive anti-tumor agents.

Locations(3)

The First Affiliated Hospital of Fujian Medical University

Xiamen, Fujian, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Shanxi Provincial People's Hospital

Taiyuan, Shanxi, China

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NCT07350850

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