R-PMDT Regimen in Newly Diagnosed PCNSL

A Prospective, Multicenter, Open-Label, Single-Arm, Phase 2 Study to Evaluate the Efficacy and Safety of Rituximab, Pirtobrutinib, High-Dose Methotrexate, Dexamethasone, and Thiotepa (R-PMDT) in Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

A total of six cycles of the R-PMDT regimen (rituximab, pirtobrutinib, high-dose methotrexate, dexamethasone, and thiotepa) will be administered to patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The primary objective is to assess the overall response rate (ORR) of R-PMDT. Secondary objectives include evaluating the complete response rate, progression-free survival (PFS), overall survival (OS), and safety.

Study Overview

• Status: Recruiting
• Conditions: Primary Central Nervous System (CNS) Lymphoma
• Intervention / Treatment: Drug: R-PMDT

Detailed Description

In this prospective, multicenter, open-label, single-arm phase 2 clinical trial, eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL) will receive six cycles of the R-PMDT regimen. The R-PMDT regimen is administered as follows: rituximab (R, 375 mg/m²) is given as an intravenous infusion on day 0; methotrexate (M, 3.5 g/m²) is administered as a 3-hour intravenous infusion on day 1, with dose adjustment based on pre-treatment creatinine clearance; dexamethasone (D, 20 mg) is given intravenously on days 1-4; thiotepa (T, 30 mg/m²) is administered intravenously on day 1; and pirtobrutinib (P, 200 mg once daily) is taken orally on days 4-21. After completion of six cycles, depending on the investigator's decision, patients may receive consolidation or maintenance therapy, including but not limited to autologous hematopoietic stem cell transplantation, radiotherapy, or pirtobrutinib maintenance. The primary objective is to assess the overall response rate (ORR) of R-PMDT. Secondary objectives include evaluation of the complete response rate, progression-free survival (PFS), overall survival (OS), and safety.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Liu, Docter; Phone Number: 86-022-23608461; Email: liuwei@ihcams.ac.cn
• Study Contact Backup: Name: Dehui Zou, Docter

Study Locations

• China
  • Tianjin, China, 022
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital
    • Contact: Shuo Chen; Phone Number: 022-23909095; Email: ec@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed primary central nervous system diffuse large B-cell lymphoma
• Adequate hematologic function: ANC ≥1.0×10⁹/L, PLT ≥75×10⁹/L
• Adequate hepatic function: ALT/AST ≤3×ULN; total bilirubin ≤1.5×ULN
• Adequate renal function: serum creatinine ≤2×ULN or CrCl ≥40 mL/min
• LVEF ≥55% by echocardiography
• Baseline oxygen saturation >92% on room air
• Expected survival ≥3 months

Exclusion Criteria:

• Prior anti-lymphoma therapy other than corticosteroids.
• Uncontrolled significant cardiovascular or cerebrovascular disease.
• Uncontrolled active systemic bacterial, fungal, or viral infection.
• Active hepatitis B and/or active hepatitis C (HCV RNA positive). Patients with positive hepatitis B surface antigen and/or core antibody but HBV-DNA < 1000 IU/mL may be included and should receive concurrent oral antiviral prophylaxis against HBV reactivation.
• Hypersensitivity to any study drug or its components.
• Other active malignancy, except for adequately controlled non-melanoma skin cancer, in situ carcinoma, or malignancy that has been in complete remission for ≥5 years.
• Pregnant or lactating women. Fertile patients unwilling to use effective contraception.
• Other conditions deemed inappropriate by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R-PMDT; Eligible patients will receive six cycles of the R-PMDT regimen.	Drug: R-PMDT; Rituximab (375 mg/m², IV infusion) is given on day 0; methotrexate (3.5 g/m², IV infusion over 3 hours) on day 1; dexamethasone (20 mg, IV infusion) on days 1-4; thiotepa (30 mg/m², IV infusion) on day 1; and pirtobrutinib (200 mg, oral) on days 4-21 or until the day prior to methotrexate administration in the next cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The proportion of subjects achieving either a complete response (CR) or partial response (PR) after treatment with R-PMDT, as assessed by the Lugano criteria.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free-Survival (PFS)	From the date of the first dose of therapy is given until disease progression, death or last follow-up	up to 2 years
Complete response rate (CRR)	The proportion of subjects achieving a CR after treatment with R-PMDT, as assessed by the Lugano criteria.	up to 2 years
Overall survival (OS)	From the date of the first dose of therapy to the date of death from any cause.	up to 2 years

Collaborators and Investigators

• Sponsor: Zou Dehui

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): May 20, 2028
• Study Completion (Estimated): May 20, 2030

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PCNSL; R-PMDT
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma
• Other Study ID Numbers: LBCL-RPMDT1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No