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

Sponsor
Tongji Hospital
Study ID
NCT07350850
Phase
PHASE2
Status
Recruiting
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Conditions

  • PCNSL
  • Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pirtobrutinib, Sintilimab, Rituximab, Methotrexate — DRUG
    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.
  • Standard of Care (Investigator Selected) — DRUG
    Patients eligible for curative-intent therapy will receive one of the following three guideline-recommended, high-dose methotrexate (HD-MTX)-based first-line regimens, selected by the treating physician based on patient age, performance status, comorbidities, and clinical judgment: MATRix Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Cytarabine 2 g/m² IV twice daily on Days 2-3; Thiotepa 30 mg/m² orally on Day 4. Cycle length: 21 days, up to 6 cycles. RMT Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Temozolomide 150 mg/m² orally once daily on Days 1-5. Cycle length: 21 days, up to 6 cycles. MR-BTKi Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Covalent BTK inhibitor (Ibrutinib 560 mg qd, Zanubrutinib 160 mg bid, or Orelabrutinib 150 mg qd) orally on Days 1-21. Cycle length: 21 days, up to 6 cycles.

Study Details

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 Dates

Start date
Dec 25, 2025
Status verified
May 2026
Primary completion
Dec 31, 2028
Completion
Jun 30, 2029

Study Design

Enrollment
77 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Interventional Cohort
    Patients receive Rituximab, Methotrexate, Sintilimab, and Pirtobrutinib for 6 cycles (21 days/cycle).
  • Active Comparator: Active Comparator Cohort
    Patients eligible for curative-intent therapy will receive one of the following three guideline-recommended, high-dose methotrexate (HD-MTX)-based first-line regimens, selected by the treating physician based on patient age, performance status, comorbidities, and clinical judgment: MATRix Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Cytarabine 2 g/m² IV twice daily on Days 2-3; Thiotepa 30 mg/m² orally on Day 4. Cycle length: 21 days, up to 6 cycles. RMT Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Temozolomide 150 mg/m² orally once daily on Days 1-5. Cycle length: 21 days, up to 6 cycles. MR-BTKi Regimen: Rituximab 375 mg/m² IV on Day 0; Methotrexate 3.5 g/m² IV on Day 1; Covalent BTK inhibitor (Ibrutinib 560 mg qd, Zanubrutinib 160 mg bid, or Orelabrutinib 150 mg qd) orally on Days 1-21. Cycle length: 21 days, up to 6 cycles.

Primary Outcome Measure

Complete Response Rate (CRR) [ Time Frame: At the completion of induction treatment(approximately 18 weeks) ]

Central Contacts

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