Primary Central Nervous System LymphomaDiffuse Large B-Cell Lymphoma
Investigational drug(s) / intervention(s)
PenpulimabRituximabMethotrexateCytarabine
Penpulimab: Anti-PD-1 monoclonal antibody, 200 mg intravenously on Day 5 of each induction cycle; continued as maintenance in responders.
Rituximab: 375 mg/m2 intravenously on Day 0 of each induction cycle.
Methotrexate: 3.5 g/m2 intravenously on Day 1 of each induction cycle.
Cytarabine: Age \<60 or ECOG ≤2: 2 g/m2 q12h on Days 2-3; age ≥60 or ECOG \>2: 1 g/m2 q12h on Day 2 (from cycle 2).
Study summary
This is a prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm (R-MA: rituximab, methotrexate, cytarabine). Induction is administered every 21 days for 6 cycles, followed by risk- and response-adapted consolidation (ASCT or whole-brain radiotherapy) and penpulimab maintenance. The primary objective is to compare the 2-year progression-free survival rate between the two arms.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
1. Fully understands the study and voluntarily signs informed consent.
2. Age 18 to 80 years.
3. Treatment-naive, pathologically (immunophenotypically) confirmed PCNSL (per 2016 WHO classification).
4. Diffuse large B-cell lymphoma originating in the CNS without other organ involvement, confirmed by PET-CT or contrast-enhanced CT.
5. Expected survival more than 3 months.
6. Laboratory: creatinine clearance ≥50 mL/min (Cockcroft-Gault); INR ≤1.5 x ULN or aPTT ≤1.5 x ULN (INR 2-3 allowed if on warfarin); LVEF ≥50%.
7. GFR ≥60 mL/min.
8. Participants of childbearing potential must agree to use effective contraception during the study and for 30 days after the last dose.
Exclusion Criteria:
1. Contraindication to any study drug.
2. Clinically significant liver disease, including viral or other hepatitis or cirrhosis (active HBV or active hepatitis C as defined).
3. HIV infection.
4. History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of penpulimab.
5. Prior anti-PD-1/PD-L1/PD-L2, anti-CTLA-4 antibody, CAR-T, or any other agent targeting T-cell co-stimulation or checkpoint pathways.
6. Congestive heart failure (NYHA \>2); acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months.
7. Congenital long QT syndrome or QTcF \>480 ms.
8. Other malignancy within the past 5 years (except adequately treated in situ cervical carcinoma, basal cell skin carcinoma, in situ breast carcinoma, or a second primary cancer cured and recurrence-free for 5 years).
9. Pregnant or lactating women, or intending to become pregnant during the study.
10. History of clinically significant neurological or psychiatric disorder, or substance/drug abuse.
11. Clinically significant active infection.
Primary outcome measure(s)
2-year progression-free survival (PFS) rate — 2 years from randomization PFS is defined as the time from randomization to first documented disease progression or relapse (per 2014 Lugano response criteria) or death from any cause, whichever occurs first, as determined by the investigator.
Trial sites (5)
Facility
City
Region
Status
The First People's Hospital of Changzhou
Changzhou
Jiangsu
The First People's Hospital of Huai'an
Huai'an
Jiangsu
The First Affiliated Hospital of Nanjing Medical University
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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