Testing a four-drug regimen (methotrexate, rituximab, sintilimab, pirtobrutinib) versus investigator-selected care for newly diagnosed PCNSL

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter Phase 2 program that enrolls treatment‑naive adults with primary central nervous system lymphoma into an interventional cohort receiving high‑dose methotrexate plus rituximab, the anti‑PD‑1 antibody sintilimab, and the reversible BTK inhibitor pirtobrutinib, alongside a real‑world observational cohort receiving investigator‑selected standard treatments. The study will measure complete remission rate as a primary outcome and will track safety, tolerability, and survival outcomes over follow‑up. The combination aims to pair the cytotoxic backbone of methotrexate and rituximab with improved CNS‑penetrant BTK inhibition and PD‑1 blockade to target common molecular drivers in PCNSL. Sites are enrolled across several major hospitals in China to capture real‑world comparator data alongside the experimental regimen.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age \>= 18 years.
2. Voluntarily signed informed consent.
3. ECOG Performance Status 0-3.
4. Expected survival \> 3 months.
5. Histopathologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) restricted to the CNS or eyes (PCNSL).
6. Measurable lesion on contrast-enhanced MRI (\>10x10 mm) or positive CSF cytology for leptomeningeal disease.
7. No prior systemic treatment for lymphoma (corticosteroids excepted).
8. Adequate bone marrow and organ function (ANC \>=1.5x10\^9/L, PLT \>=80x10\^9/L, Hb \>=80 g/L; Bilirubin \<=1.5xULN, AST/ALT \<=2.5xULN; Creatinine \<=1.5xULN or CrCl \>=60 mL/min) .
9. Stable controlled comorbidities allowed (e.g., hypertension with blood pressure \<=160/100 mmHg, type 2 diabetes with HbA1c \<=8%, mild coronary heart disease without myocardial infarction in the past 6 months).
10. Basic communication ability to complete PROs questionnaires (no severe cognitive impairment).
11. Reproductive-aged females and males with childbearing potential: No pregnancy plans during the study and 3 months after treatment discontinuation; use effective contraception (abstinence, physical contraception, or hormonal contraceptives initiated \>=3 months before first dose). Males prohibited from donating sperm during treatment and 3 months after discontinuation.
12. For Observational Cohort (Palliative Care Subgroup only): Pathologically confirmed DLBCL restricted to the CNS or eyes; Follow-up available for efficacy assessment (at least one CR evaluation) .

Exclusion Criteria:

1.Prior treatment with PD-1/PD-L1 inhibitors or CTLA4 monoclonal antibodies. Uncontrolled active infection. 2.Uncontrolled or significant cardiovascular diseases: 3.Congestive heart failure (NYHA class III/IV),

1. myocardial infarction, unstable angina within 6 months before first dose; arrhythmia requiring treatment; LVEF \<50%.
2. Primary cardiomyopathy.
3. History of clinically significant QTc prolongation, second-degree type II/third-degree atrioventricular block, or QTc interval (Fridericia method) \>470 msec (females) / \>480 msec (males).
4. Atrial fibrillation (EHRA grade ≥2b).
5. Refractory hypertension. 4.Active hepatitis B/C infection (HBV-DNA ≥ detection limit, HCV RNA positive) or syphilis. (Exceptions: HBV-DNA \< detection limit, cured HCV).

5.HIV infection. 6.Prior organ transplantation or allogeneic stem cell transplantation. 7.Pregnant or lactating females. 8.Prior/current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, or radiation pneumonitis (unsuitable for study per investigator).

9.Autoimmune diseases requiring systemic treatment within 2 years. 10.For Observational Cohort (Palliative Care Subgroup only): Incomplete clinical data (e.g., no pathological report, inability to perform MRI/PET-CT assessment).

Where it's running

• The First Affiliated Hospital of Fujian Medical University
  Xiamen, Fujian, China Recruiting
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  Wuhan, Hubei, China Recruiting
• China-Japan Union Hospital of Jilin University
  Changchun, Jilin, China Recruiting
• Shanxi Provincial People's Hospital
  Taiyuan, Shanxi, China Not yet recruiting

Study contacts

• Study coordinator: Jia Wei, MD
• Email: jiawei@tjh.tjmu.edu.cn
• Phone: 027-83663200

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.