PD-1 Inhibitor Combined With Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL.

NCT07410520 | Recruiting Phase 2

• 1 other identifier: 2025-SR-646
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, single-arm, prospective clinical study of PD-1 inhibitor combined with rituximab, methotrexate, and orelabrutinib (PD-1i+RMO) in the treatment of newly diagnosed primary central nervous system lymphoma (ND-PCNSL) and secondary central nervous system lymphoma (SCNSL). The primary endpoint is 1-year progression-free survival (PFS).

Conditions

Primary Central Nervous System Lymphoma (PCNSL); Secondary Central Nervous System Lymphoma (SCNSL)

Keywords

PD-1 Inhibitor; Rituximab; Methotrexate; Orelabrutinib

Outcome Measures

Primary Outcomes (1)

• 1 year Progression free survival (PFS)

  PFS is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.

  From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Secondary Outcomes (3)

• 1 year overall survival (OS)

  From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 1 year

• Overall response rate (ORR)

  At the end of induction therapy

• Adverse Events

  1 year

Study Arms (1)

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

EXPERIMENTAL

Drug: PD -1/PD-L1 monoclonal antibody; Drug: Rituximab (R); Drug: Methotrexate; Drug: Orelabrutinib; Procedure: ASCT/WBRT

Interventions

PD -1/PD-L1 monoclonal antibody DRUG

Induction Phase: Intravenous infusion, day2, cycle1-8(Cycles: every 3 weeks) Maintenance Phase: continued every 2 months for 2 years.

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

Rituximab (R) DRUG

Induction Phase: 375mg/m2, Intravenous infusion, day0, cycle1-8(Cycles: every 3 weeks)

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

Methotrexate DRUG

Induction Phase: 3.5g/m2, Intravenous infusion, day1, cycle1-8(Cycles: every 3 weeks)

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

Orelabrutinib DRUG

Induction Phase: 150mg qd(after methotrexate levels are cleared to \< 0.1 μmol/L.), cycle1-8(Cycles: every 3 weeks) Maintenance Phase: 150mg qd for 2 years.

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

ASCT/WBRT PROCEDURE

Patients with PR, SD, or PD after 8 cycles will discontinue the study, while those achieving CR will be evaluated by investigators for autologous stem cell transplantation (ASCT) or whole-brain radiotherapy (WBRT).

PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO)

Eligibility Criteria

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

You may qualify if:

• \[1\] Newly diagnosed PCNSL confirmed by histopathology, or independently relapsed SCNSL (diffuse large B-cell lymphoma), diagnosed according to the 2016 WHO diagnostic criteria.
• \[2\] Signed written informed consent, and ability to comply with protocol-specified visits and related procedures.
• \[3\] Cranial MRI (non-contrast + contrast) performed within 28 days prior to study enrollment must show at least one measurable lesion in two perpendicular dimensions (according to the 2014 Lugano criteria).
• \[4\] ECOG performance status of 0-4. \[5\] Adequate organ and bone marrow function, defined as follows:
• Hematology: Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L, platelet count (PLT) ≥ 50×10⁹/L, hemoglobin (HGB) ≥ 8.0 g/dL; no administration of granulocyte growth factors, platelet transfusion, or red blood cell transfusion within 7 days prior to testing.
• Liver function: Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
• Renal function: Serum creatinine (Cr) ≤ 1 × ULN or creatinine clearance (CCr) ≥ 90 mL/min.
• Cardiac function: Cardiac function class below Grade III (NYHA criteria); echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%.
• Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ ULN + 10 s, and prothrombin time (PT) ≤ ULN + 3 s.
• Thyroid function: Baseline thyroid-stimulating hormone (TSH) level within normal range, or abnormal baseline TSH with normal T3/T4 and no associated symptoms.
• \[6\] Life expectancy \> 3 months. \[7\] Age ≥ 18 years. \[8\] Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last dose.

You may not qualify if:

• Presence of disease involvement outside the central nervous system.
• History of a second primary malignancy (except for adequately treated non-melanoma skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, intramucosal carcinoma of the gastrointestinal tract, or breast carcinoma that has been cured and has shown no recurrence within the past 5 years).
• History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of the PD-1 monoclonal antibody injection formulation.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or CAR-T cell therapy (or any other antibody targeting T-cell co-stimulation or checkpoint pathways).
• Previous allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Planned to receive other systemic anti-tumor therapies during the study period.
• Use of anti-cancer vaccines or other immunostimulatory anti-tumor therapy within 3 months before the first dose.
• Severe acute or chronic infection requiring systemic therapy.
• Active, known, or suspected autoimmune disease (refer to Appendix 5), or history of such disease within the past 2 years (patients with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in the past 2 years, hypothyroidism requiring only thyroid hormone replacement, or type 1 diabetes requiring only insulin replacement may be enrolled).
• Use of immunosuppressive drugs within 4 weeks prior to the first study treatment, excluding intranasal, inhaled, or other local glucocorticoids or physiologic doses of systemic glucocorticoids (i.e., no more than 10 mg/day prednisone or equivalent).
• Positive human immunodeficiency virus antibody (HIV-Ab), active hepatitis, or other uncontrolled infectious diseases.
• Current or previous history of idiopathic pulmonary fibrosis or idiopathic pneumonia.
• Known active tuberculosis.
• Previous history of grade ≥3 immune-related adverse events from prior immunotherapy.
• History of definite neurological or psychiatric disorders.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Interventions

Rituximab; Methotrexate; orelabrutinib

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

Central Study Contacts

Lei Fan

CONTACT

+8613813976136; fanlei3014@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2026
• First Posted: February 13, 2026
• Study Start: February 7, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)