Rituximab, Methotrexate, and Tepadina Induction Followed by Etoposide and Cytarabine Consolidation in Primary Central Nervous System Lymphoma

FengYan Jin41 enrolled

Overview

High-dose methotrexate (HD-MTX) remains the foundation of treatment for primary central nervous system lymphoma (PCNSL), but outcomes are suboptimal. The addition of rituximab has shown mixed results, partly due to limited blood-brain barrier penetration. The MATRix regimen (rituximab, HD-MTX, cytarabine, thiotepa) has improved survival but is associated with significant toxicity. Consolidation therapy is recommended after induction, but there is no standard approach. Preliminary data suggest that etoposide and cytarabine (EA) consolidation after rituximab-HD-MTX induction may offer improved tolerability, though relapse rates remain high. This study evaluates the safety, efficacy, and tolerability of a novel RMT-EA regimen-rituximab, methotrexate, and thiotepa (RMT) induction followed by etoposide and cytarabine (EA) consolidation-in newly diagnosed, untreated PCNSL patients. The aim is to improve remission depth and prolong disease-free survival, especially in younger patients.

A retrospective analysis conducted at the study center demonstrated an objective response rate (ORR) of 64.3% among patients with primary central nervous system lymphoma (PCNSL) receiving chemotherapy. This prospective, single-arm clinical study is designed to evaluate the safety, efficacy, and tolerability of a novel treatment regimen-rituximab, methotrexate, and thiotepa (RMT) for induction, followed by etoposide and cytarabine (EA) for consolidation-in patients with newly diagnosed PCNSL. The study hypothesizes that the RMT-EA regimen will increase the ORR to 84% while maintaining an acceptable safety profile. The goal is to generate additional evidence to support the optimization of frontline therapy for PCNSL, with a focus on improving remission depth, minimizing relapse rates, and extending progression-free survival, particularly in younger patient populations.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

Rituximab, Methotrexate, and Thiotepa (R-MT) Induction Followed by Etoposide and Cytarabine (EA) ConsolidationDRUG

Pre-induction Therapy (R-M regimen): Cycle 1-2 (C1-C2): Rituximab (R): 375 mg/m² IV, on Day 1 Methotrexate (MTX): 3.5 g/m² IV over 3 hours, on Day 2 Induction Therapy (R-MT regimen): Cycle 3-6 (C3-C6): Rituximab (R): 375 mg/m² IV, on Day 1 Methotrexate (MTX): 3.5 g/m² IV over 3 hours, on Day 2 Thiotepa (T): 30 mg/m² IV over 30 minutes, on Day 3 Consolidation Therapy (EA regimen): Cycle 7-8 (C7-C8): Etoposide (E): 5 mg/kg IV, every 12 hours on Days 1 and 2 Cytarabine (A): 2.0 g/m² IV over 2 hours, every 12 hours on Days 3 and 4

Eligibility

Sex: ALLMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≤ 60 years, male or female * Histologically and immunohistochemically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) without prior treatment * No evidence of systemic lymphatic or hematopoietic involvement or other systemic disease, based on thorough physical examination and imaging/laboratory tests * Diagnosis meets criteria for Primary Central Nervous System Lymphoma (PCNSL) * Written informed consent obtained from the patient or their legal guardian * Voluntary agreement to participate in the study Exclusion Criteria: * Presence of another active malignancy * Known history of HIV infection or diagnosis of acquired immunodeficiency syndrome (AIDS) * Known allergy to any of the investigational drugs or their excipients * Any condition that, in the opinion of the investigator, may lead to early study termination, including but not limited to: * Severe comorbidities * Significant laboratory abnormalities * Serious social or family circumstances affecting safety or compliance

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

Objective Response Rate (ORR): Defined as the proportion of participants who achieve Complete Remission (CR), Unconfirmed Complete Remission (CRu), or Partial Remission (PR) according to the International Primary CNS Lymphoma Collaborative Group (IPCG) efficacy assessment criteria.

Time frame: From the date of enrollment until the end of induction and consolidation treatment, assessed up to approximately 8 months.

Secondary Outcomes

Progression-Free Survival (PFS)

Progression-Free Survival (PFS):Defined as the time from the start of treatment to the first occurrence of disease progression, treatment failure, or death. Disease progression or failure will be defined according to the International Primary CNS Lymphoma Collaborative Group (IPCG) efficacy assessment criteria.

Time frame: From the start of treatment until the first documented disease progression, treatment failure, or death, assessed up to 36 months.

Overall Survival (OS)

Overall Survival (OS): Defined as the time from study enrollment to death from any cause.

Time frame: From the date of study enrollment until death from any cause, assessed up to 36 months.

Cause of Death

Disease-related Death: Includes death due to lymphoma or acute toxicity from treatment. Other Causes: Includes death due to cardiovascular disease, infections, accidents, second primary malignancies, undetermined mixed causes, or unknown causes.

Time frame: From the date of study enrollment until death, categorized by cause, assessed up to 36 months.

Safety(Toxicity, AE, SAE))

Toxicity Reactions: Graded according to the NCI CTCAE (version 5.0) criteria, with the investigator determining whether the toxicity is treatment-related. Adverse Events (AE): Events that lead to an interruption of treatment for more than 3 days, or early termination of the study. Serious Adverse Events (SAE): Defined as per Section 5.1 of the protocol. Supportive Treatment: Any treatments administered to address toxicity reactions.

Time frame: Monitored throughout the treatment period and until the end of the safety follow-up period, assessed up to approximately 12 months.