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

NCT ID: NCT06946407

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-02
• Study Completion Date: 2029-12-01

Brief Summary

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.

Detailed Description

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.

Conditions

Primary Central Nervous System Lymphoma (PCNSL); CNS Lymphoma Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Evaluation of Objective Response Rate (ORR) with RMT-EA as First-Line Treatment for PCNSL

This arm evaluates the RMT-EA regimen for first-line treatment of newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).

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 This study arm is designed to assess the Objective Response Rate (ORR), as well as the safety, efficacy, and quality of life outcomes of the RMT-EA regimen in patients with newly diagnosed PCNSL aged ≤60 years. The dosing schedules and drug combinations outlined above distinguish this arm from others in the study.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FengYan Jin

OTHER

Sponsor Role: lead

Responsible Party

FengYan Jin

Clinical Professor of Hematology Department

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Facility Name: The First Hospital of Jilin University

Changchun, , China

Site Status: RECRUITING

Countries

China

Facility Contacts

Jin Fengyan Fengyan Jin, Professor

Role: primary

fengyanjin@jlu.edu.cn

+8613844989638

Other Identifiers

PCNSL-RMTEA

Identifier Type: -

Identifier Source: org_study_id