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

Recruiting now · Phase 2

Conditions studied: PCNSL, Primary Central Nervous System Lymphoma

In brief

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

Key facts

Study ID

NCT07350850

Run by

Tongji Hospital

People needed

77

Starts

2025-12-25

Expected to finish

2029-06-30

Last updated by the study team

2026-06-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age >= 18 years.
• Voluntarily signed informed consent.
• ECOG Performance Status 0-3.
• Expected survival > 3 months.
• Histopathologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) restricted to the CNS or eyes (PCNSL).
• Measurable lesion on contrast-enhanced MRI (>10x10 mm) or positive CSF cytology for leptomeningeal disease.
• No prior systemic treatment for lymphoma (corticosteroids excepted).
• 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) .
• 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).
• Basic communication ability to complete PROs questionnaires (no severe cognitive impairment).
• 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.
• 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) .

You may not qualify if…

• 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),
• myocardial infarction, unstable angina within 6 months before first dose; arrhythmia requiring treatment; LVEF <50%.
• Primary cardiomyopathy.
• 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).
• Atrial fibrillation (EHRA grade ≥2b).
• Refractory hypertension. 4.Active hepatitis B/C infection (HBV-DNA ≥ detection limit, HCV RNA positive) or syphilis. (Exceptions: HBV-DNA < detection limit, cured HCV).
• 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).
• 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 is running

• The First Affiliated Hospital of Fujian Medical University — Xiamen, Fujian, China (enrolling)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (enrolling)
• China-Japan Union Hospital of Jilin University — Changchun, Jilin, China (enrolling)
• Shanxi Provincial People's Hospital — Taiyuan, Shanxi, China

Full record on ClinicalTrials.gov

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