R-MA-PD-1 Versus R-MA in Treatment-naive Primary CNS Lymphoma

NCT07764601 | Not Yet Recruiting

• 2 other identifiers: RM-MA-PD12026-SR-532
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Primary Central Nervous System Lymphoma; Diffuse Large B-Cell Lymphoma

Keywords

PCNSL; Penpulimab; PD-1 inhibitor; High-dose methotrexate; Rituximab

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free survival (PFS) rate

  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.

  2 years from randomization

Secondary Outcomes (5)

• Complete response (CR) rate

  From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)

• Objective response rate (ORR)

  From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)

• Overall survival (OS)

  Up to 3 years from randomization

• Duration of response (DOR)

  Up to 3 years from randomization

• Incidence of adverse events

  From first dose until 30 days after last dose (induction 18 weeks + consolidation [ASCT/WBRT] + penpulimab maintenance 24 weeks)

Study Arms (2)

R-MA-PD-1 (Experimental)

EXPERIMENTAL

Rituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), cytarabine (D2-3 or D2 by age/ECOG), plus penpulimab 200 mg (D5), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation and penpulimab maintenance.

Biological: Penpulimab; Drug: Rituximab; Drug: Methotrexate; Drug: Cytarabine

R-MA (Active Comparator)

ACTIVE COMPARATOR

Rituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), and cytarabine (D2-3 or D2 by age/ECOG), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation (ASCT or WBRT).

Drug: Rituximab; Drug: Methotrexate; Drug: Cytarabine

Interventions

Penpulimab BIOLOGICAL

Anti-PD-1 monoclonal antibody, 200 mg intravenously on Day 5 of each induction cycle; continued as maintenance in responders.

R-MA-PD-1 (Experimental)

Rituximab DRUG

375 mg/m2 intravenously on Day 0 of each induction cycle.

R-MA (Active Comparator); R-MA-PD-1 (Experimental)

Methotrexate DRUG

3.5 g/m2 intravenously on Day 1 of each induction cycle.

R-MA (Active Comparator); R-MA-PD-1 (Experimental)

Cytarabine DRUG

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).

R-MA (Active Comparator); R-MA-PD-1 (Experimental)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fully understands the study and voluntarily signs informed consent.
• Age 18 to 80 years.
• Treatment-naive, pathologically (immunophenotypically) confirmed PCNSL (per 2016 WHO classification).
• Diffuse large B-cell lymphoma originating in the CNS without other organ involvement, confirmed by PET-CT or contrast-enhanced CT.
• Expected survival more than 3 months.
• 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%.
• GFR ≥60 mL/min.
• Participants of childbearing potential must agree to use effective contraception during the study and for 30 days after the last dose.

You may not qualify if:

• Contraindication to any study drug.
• Clinically significant liver disease, including viral or other hepatitis or cirrhosis (active HBV or active hepatitis C as defined).
• HIV infection.
• History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of penpulimab.
• 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.
• Congestive heart failure (NYHA \>2); acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months.
• Congenital long QT syndrome or QTcF \>480 ms.
• 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).
• Pregnant or lactating women, or intending to become pregnant during the study.
• History of clinically significant neurological or psychiatric disorder, or substance/drug abuse.
• Clinically significant active infection.

Sponsors & Collaborators

• WEI XU: lead

Study Sites (5)

The First People's Hospital of Changzhou

Changzhou, Jiangsu, China

Location

The First People's Hospital of Huai'an

Huai'an, Jiangsu, China

Location

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Location

Wuxi People's Hospital

Wuxi, Jiangsu, China

Location

Yixing People's Hospital

Yixing, Jiangsu, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

penpulimab; Rituximab; Methotrexate; Cytarabine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Wei Xu

CONTACT

+86 13951699449; xuwei10000@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Department of Hematology

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 14, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 14, 2026

Record last verified: 2026-08

Locations

CN (5)