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RECRUITING

NCT07350850

PHASE2

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

Sponsor: Tongji Hospital

View on ClinicalTrials.gov

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.

Official title: 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)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

110

Start Date

2025-12-25

Completion Date

2029-06-30

Last Updated

2026-03-09

Healthy Volunteers

Conditions

PCNSL Primary Central Nervous System Lymphoma

Interventions

DRUG

Pirtobrutinib, 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.

DRUG

Standard 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.

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).

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