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

April 23, 2025 updated by: FengYan Jin

A Prospective, Single-Arm Clinical Study of Rituximab, Methotrexate, and Thiotepa (R-MT) Induction Followed by Etoposide and Cytarabine (EA) Consolidation for Primary Central Nervous System Lymphoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

41

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • China
      • Changchun, China
        • Recruiting
        • Facility Name: The First Hospital of Jilin University
        • 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

Accepts Healthy Volunteers

No

Description

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

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: 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.
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From the date of enrollment until the end of induction and consolidation treatment, assessed up to approximately 8 months.
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.
From the date of enrollment until the end of induction and consolidation treatment, assessed up to approximately 8 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From the start of treatment until the first documented disease progression, treatment failure, or death, assessed up to 36 months.
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.
From the start of treatment until the first documented disease progression, treatment failure, or death, assessed up to 36 months.
Overall Survival (OS)
Time Frame: From the date of study enrollment until death from any cause, assessed up to 36 months.

Overall Survival (OS):

Defined as the time from study enrollment to death from any cause.
From the date of study enrollment until death from any cause, assessed up to 36 months.
Cause of Death
Time Frame: From the date of study enrollment until death, categorized by cause, assessed up to 36 months.

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.
From the date of study enrollment until death, categorized by cause, assessed up to 36 months.
Safety(Toxicity, AE, SAE))
Time Frame: Monitored throughout the treatment period and until the end of the safety follow-up period, assessed up to approximately 12 months.

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

Collaborators and Investigators

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

Sponsor

FengYan Jin

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 (Actual)

December 2, 2022

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

April 9, 2025

First Submitted That Met QC Criteria

April 23, 2025

First Posted (Actual)

April 27, 2025

Study Record Updates

Last Update Posted (Actual)

April 27, 2025

Last Update Submitted That Met QC Criteria

April 23, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCNSL-RMTEA

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

product manufactured in and exported from the U.S.

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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