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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Rituximab, Methotrexate, and Thiotepa (R-MT) Induction Followed by Etoposide and Cytarabine (EA) Consolidation (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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.
次要结局
- 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.)
研究者
FengYan Jin
Clinical Professor of Hematology Department
The First Hospital of Jilin University