Pirtobrutinib Plus Methotrexate-Based Chemoimmunotherapy for Systemic DLBCL With CNS Involvement

September 10, 2026 updated by: Pengpeng Xu

Efficacy and Safety of Methotrexate (MTX) Combined With Chemoimmunotherapy Plus Pirtobrutinib in Patients With Systemic Diffuse Large B-Cell Lymphoma (DLBCL) and Central Nervous System Involvement

This is an open-label, prospective, single-arm, multicenter study designed to evaluate the efficacy and safety of MTX plus pirtobrutinib combined with routinely-used clinical chemoimmunotherapy regimens in patients with DLBCL and central nervous system (CNS) involvement.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This was an open-label, prospective, single-arm, multicenter study designed to evaluate the efficacy and safety of MTX plus pirtobrutinib combined with conventional clinical chemoimmunotherapy regimens in patients with DLBCL and central nervous system (CNS) involvement. Subjects meeting the inclusion/exclusion criteria were enrolled into the experimental arm after providing written informed consent. Each treatment cycle lasted 3 weeks. Following 6 cycles of induction therapy, subjects who failed to achieve partial response (PR) or experienced disease progression at any time point were withdrawn from the study and received salvage therapy. Subjects achieving complete response (CR) or PR proceeded to autologous stem-cell transplantation if they were young and eligible for transplantation. For patients with stable disease (SD) or progressive disease (PD), subsequent treatment was administered at the investigator's discretion, followed by follow-up observation for up to 3 years.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients must satisfy all of the following conditions to be enrolled in this study:

1.Fully understand the study and voluntarily provide written informed consent. 2.Age: 14-80 years old. 3.Estimated survival of more than 3 months as judged by the investigator. 4.Histologically or cytologically / flow-cytometry confirmed B-cell-derived diffuse large B-cell lymphoma (DLBCL).

5.Central nervous system (CNS) involvement: diagnosis is established if any one of the following is present: symptoms related to CNS involvement, abnormal imaging findings, or pathological evidence (positive cerebrospinal fluid (CSF) cytology, positive biopsy of brain parenchymal lesions, or positive CSF-ctDNA).

6.Non-hematologic toxicities related to prior therapy shall have recovered to Grade 1 or baseline (per NCI-CTCAE Version 5.0), alopecia excluded.

7.Bone marrow and organ function meet the following criteria (no blood transfusion, G-CSF administration, or pharmacologic correction within 14 days prior to screening):

  1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; platelet count ≥ 50 × 10⁹/L; hemoglobin ≥ 60 g/L.
  2. Liver function: serum total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN in the presence of liver involvement); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN in the presence of liver involvement).
  3. Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  4. Renal function: serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 30 mL/min.
  5. Calculationformula(Cockcroft-Gault):Male:Cr(mL/min) = (140 - age) × bodyweight (kg) / (72 × serum creatinine(mg/dL))Female:Cr(mL/min) = (140 - age) × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)) 8.Women of child-bearing potential and men with reproductive potential have no plan for conception with their partners during the study and for 3 months after treatment discontinuation. They must adopt one of the following effective contraceptive measures throughout the study period and for 3 months after treatment discontinuation: abstinence, physical contraception (e.g., sterilization, condoms), or hormonal contraceptives initiated at least 3 months prior to the first study drug administration. Male subjects shall refrain from sperm donation from treatment initiation through 3 months after treatment discontinuation. The patient or legal guardian voluntarily signs the informed consent form.

9.Good compliance and willingness to adhere to visit schedules, drug administration plans, laboratory tests, and other study procedures.

exclusion Criteria:

Patients meeting any one of the following criteria will be excluded from this study:

  1. Contraindication to any drug in the treatment regimen.
  2. History of active liver disease, including viral or other hepatitis, or liver cirrhosis. (Active hepatitis B is defined as HBV-DNA above the upper limit of normal; active hepatitis C is defined as positive HCV antibody. Subjects with positive HCV antibody but negative HCV-RNA are eligible for enrollment.)
  3. Human immunodeficiency virus (HIV) infection.
  4. Congestive heart failure (New York Heart Association [NYHA] functional class > 2); medical history of acute myocardial infarction, unstable angina pectoris, stroke, or transient ischemic attack within the preceding six months.
  5. Congenital long-QT syndrome, or QTc > 480 ms. (Note: QTc interval shall be calculated by the Fridericia's formula: QTcF = QT/(RR)^0.33.)
  6. Pregnant or breastfeeding women, or subjects planning to become pregnant during the study period.
  7. Documented prior history of neurological or psychiatric disorders; or history of psychotropic substance abuse or illicit drug use.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: pirtobrutinib+MTX+immunochemotherapy
Drug: pirtobrutinib+MTX+immunolchemotherapy

Induction therapy: Pirtobrutinib 200 mg once daily, combined with MTX (thiotepa for patients intolerant to MTX) plus chemoimmunotherapy regimens.

MTX 3.5 g/m² or thiotepa 30 mg/m²; R-CHOP regimen:

Rituximab 375 mg/m² Day 0 Cyclophosphamide 750 mg/m² Day 1 Doxorubicin 50 mg/m² Day 1 Vincristine 1.4 mg/m² Day 1 Prednisone 100 mg/day Days 1-5

MTX 3.5 g/m² or thiotepa 30 mg/m²; Pola-R-CHP regimen:

Rituximab 375 mg/m² Day 1 Cyclophosphamide 750 mg/m² Day 1 Doxorubicin 50 mg/m² Day 1 Prednisone 100 mg/day Days 1-5 Polatuzumab vedotin 1.8 mg/kg Day 1 Each cycle was 21 days, for a total of 6 cycles.

Consolidation therapy: After achieving CR or PR, young and transplant-eligible subjects could receive autologous stem-cell transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
CRR(complete remission rate) after 6 cycles of induction therapy
Time Frame: Week 18，at the end of induction therapy(each cycle is 21 days)
Week 18，at the end of induction therapy(each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
2-year PFS rate
Time Frame: 2 years
2 years
overall survival (OS)
Time Frame: From first study treatment until death from any cause, up to 4 years
From first study treatment until death from any cause, up to 4 years
objective response rate (ORR)
Time Frame: week 18，at the end of 6 cycles of induction therapy(each cycle is 21 days )
week 18，at the end of 6 cycles of induction therapy(each cycle is 21 days )

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pengpeng Xu

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

September 4, 2026

First Submitted That Met QC Criteria

September 4, 2026

First Posted (Actual)

September 10, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-691

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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