R-PMDT Regimen in Newly Diagnosed PCNSL

Phase 2RecruitingNCT07604987

Zou Dehui33 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Central Nervous System (CNS) Lymphoma

Interventions

R-PMDTDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, China

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: up to 2 years

Secondary Outcomes

Complete response rate (CRR)

The proportion of subjects achieving a CR after treatment with R-PMDT, as assessed by the Lugano criteria.

Time frame: up to 2 years

Progression-Free-Survival (PFS)

From the date of the first dose of therapy is given until disease progression, death or last follow-up

Time frame: up to 2 years

Overall survival (OS)

From the date of the first dose of therapy to the date of death from any cause.

Time frame: up to 2 years

Central Contacts

Wei Liu, Docter

CONTACT

86-022-23608461 liuwei@ihcams.ac.cn

Dehui Zou, Docter

CONTACT

Data from ClinicalTrials.gov

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