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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Facility Name: The First Hospital of Jilin University | Recruiting | Changchun | China |
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| Overall Survival (OS) | 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 | 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)) | 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. |
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D008727 | Methotrexate |
| D013852 | Thiotepa |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D013721 | Triethylenephosphoramide |
| D001388 | Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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