Clinical trial NCT06946407: Rituximab, Methotrexate, and Tepadina Induction Followed by Etoposide and Cytarabine Consolidation in Primary Central Nervous System Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Central Nervous System Lymphoma (PCNSL)
CNS Lymphoma Treatment
Keywords: PCNSL
Induction Therapy
Consolidation Therapy
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
First posted: 2025-04-27
Enrollment: 41
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From the date of enrollment until the end of induction and consolidation treatment, assessed up to approximately 8 months.
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From the start of treatment until the first documented disease progression, treatment failure, or death, assessed up to 36 months.
measure: Overall Survival (OS)
timeFrame: From the date of study enrollment until death from any cause, assessed up to 36 months.
measure: Cause of Death
timeFrame: From the date of study enrollment until death, categorized by cause, assessed up to 36 months.
measure: Safety(Toxicity, AE, SAE))
timeFrame: Monitored throughout the treatment period and until the end of the safety follow-up period, assessed up to approximately 12 months.
Other outcomes:
Locations:
city: Changchun
country: China
facility: Facility Name: The First Hospital of Jilin University
Study officials:
References: