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

NCT06946407 | Recruiting DMC

• 1 other identifier: PCNSL-RMTEA
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

PCNSL; Induction Therapy; Consolidation Therapy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

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

• Overall Survival (OS)

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

• Cause of Death

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

• Safety(Toxicity, AE, SAE))

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

Study Arms (1)

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

EXPERIMENTAL

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

Interventions

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

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

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• FengYan Jin: lead

Study Sites (1)

Facility Name: The First Hospital of Jilin University

Changchun, China

RECRUITING

MeSH Terms

Interventions

Rituximab; Methotrexate; Thiotepa; Cytarabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor of Hematology Department

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 27, 2025
• Study Start: December 2, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

CN (1)