Actively Recruiting
A Multicenter Prospective Study Comparing Methotrexate Combined With Rituximab, Sintilimab, and Pirtobrutinib Versus Standard High-Dose Methotrexate-Based Care in Newly Diagnosed PCNSL
Led by Tongji Hospital · Updated on 2026-06-02
77
Participants Needed
4
Research Sites
25 weeks
Total Duration
On this page
Sponsors
T
Tongji Hospital
Lead Sponsor
S
Shanxi Provincial People's Hospital
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a new four-drug combination as a first treatment for adults 18 years and older with newly diagnosed primary central nervous system lymphoma (PCNSL), a rare form of lymphoma affecting the brain and eyes. This study aims to see if combining pirtobrutinib, sintilimab, rituximab, and high-dose methotrexate can improve the complete response rate compared to standard high-dose methotrexate-based treatments, while also assessing safety and tolerability. The research compares this new treatment to commonly used regimens chosen by doctors to improve patient outcomes. Participants receive either the experimental four-drug combination or one of three standard treatment options selected by their doctor, each given in 6 cycles lasting 21 days each. The experimental group receives rituximab, methotrexate, sintilimab, and pirtobrutinib with specific dosing schedules, while the standard treatments include various combinations of rituximab, methotrexate, cytarabine, temozolomide, or covalent BTK inhibitors. Some patients may also receive additional consolidation or maintenance therapy depending on their response. Throughout the study, participants undergo regular clinical assessments including brain MRI scans with contrast, blood tests, and cerebrospinal fluid exams. They complete quality-of-life questionnaires at set points during and after treatment. Researchers monitor treatment response, progression-free and overall survival, adverse events, and patient-reported outcomes. Follow-up lasts up to two years after treatment to assess long-term effects and disease progression, with some outcomes tracked up to five years.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Voluntarily signed informed consent
- ECOG Performance Status between 0 and 3
- Expected survival longer than 3 months
- Histologically confirmed diffuse large B-cell lymphoma limited to the CNS or eyes (PCNSL)
- Measurable lesion on contrast-enhanced MRI larger than 10x10 mm or positive cerebrospinal fluid cytology for leptomeningeal disease
- No prior systemic lymphoma treatment except corticosteroids
- Adequate bone marrow and organ function as defined by specific blood counts and lab values
- Stable controlled comorbidities such as hypertension, type 2 diabetes, or mild coronary heart disease
- Ability to communicate and complete patient-reported outcome questionnaires
- Use of effective contraception during the study and for three months after treatment if of childbearing potential
You will not qualify if you...
- Prior treatment with PD-1/PD-L1 inhibitors or CTLA4 monoclonal antibodies
- Uncontrolled active infections
- Significant cardiovascular diseases including congestive heart failure (NYHA III/IV), recent myocardial infarction, unstable angina, arrhythmias needing treatment, or low left ventricular ejection fraction
- Primary cardiomyopathy or history of significant QTc prolongation and serious heart conduction abnormalities
- Atrial fibrillation of EHRA grade 2b or higher
- Refractory hypertension
- Active hepatitis B or C infection or syphilis (except controlled cases)
- HIV infection
- Prior organ or stem cell transplantation
- Pregnancy or lactation
- Current or prior lung diseases such as pulmonary fibrosis or radiation pneumonitis unsuitable for study
- Autoimmune diseases requiring systemic treatment within the past 2 years
- Incomplete clinical data or inability to perform necessary imaging assessments for the observational cohort
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 18 weeks
Participants receive assigned drug treatments in cycles every 21 days for up to 6 cycles. In the experimental group, participants receive Rituximab, Methotrexate, Sintilimab, and Pirtobrutinib. In the comparator group, participants receive one of three standard high-dose methotrexate-based regimens selected by their physician.
Up to 6 cycles with visits every 3 weeks
Duration - Up to 5 years
Participants are monitored for safety, response duration, progression-free and overall survival, and patient-reported outcomes for up to 5 years after treatment completion.
Visits every 3 months for up to 2 years for patient-reported outcomes and longer-term survival monitoring
Trial Site Locations
Total: 4 locations
1
The First Affiliated Hospital of Fujian Medical University
Xiamen, Fujian, China
Actively Recruiting
2
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China, 430000
Actively Recruiting
3
China-Japan Union Hospital of Jilin University
Changchun, Jilin, China, 130033
Actively Recruiting
4
Shanxi Provincial People's Hospital
Taiyuan, Shanxi, China, 030012
Not Yet Recruiting
Research Team
J
Jia Wei, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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