Intermediate Dose of IV MTX as CNS Prophylaxis for High Risk DLBCL

Study Overview
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Brief Summary
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Central nervous system (CNS) relapse is a devastating event of diffuse large B cell lymphoma (DLBCL). It occurs in 4%-7% of DLBCL in general and the rate is considerably higher in high-risk patients, resulting in a poor outcome.Effective methods of CNS prophylaxis have not yet been developed. Evidence for intrathecal or intravenous MTX are both controversial. In one previous study of PUMCH, IV MTX at a dose of 1g/m2 could significantly decrease the 2 year CNS relapse rate of high risk DLBCL(1.1% vs 12.1% for historic cohort, P=0.003). In current study, the investigators are aiming to confirm its efficacy through phase III study with intrathecal MTX as the controlled arm.

Detailed Description
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In this prospective, phase III, multicenter, randomized, controlled study, the investigatirs aim to compare the efficacy of intravenous MTX(IV arm) at a dose of 1g/m2 with intrathecal MTX(IT arm) in terms of preventing CNS relapse. All the patients will recieve RCHOP regimen as front-line treatment of DLBCL. Patients in IV arm will recieve 4 course of IV MTX, which is incorporated into the RCHOP, naming R-MTX-CHOP regimen. Patients in IT arm will be given intrathecal MTX for 4 courses (one time for each course). 2 year CNS relapse rate is the primary endpoint while 2 year PFS, 2 year OS and safety are the secondary endpoint.

Official Title
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Intravenous Methotrexate 1g/m2 as Central Nervous System Prophylaxis for High Risk Diffuse Large B Cell Lymphoma: a Prospective, Phase III, Randomized, Controlled Study

Conditions
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Diffuse Large B Cell Lymphoma, Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years with high CNS risk, which was defined as involvement of more than one extranodal site, or involvement of particular extranodal sites such as bone marrow, breasts, testes, paranasal sinuses, epidural space, adrenal glands, kidney and female genital system; first-line treatment planned to be RCHOP absence of CNS involvement at presentation Exclusion Criteria: primary CNS lymphoma already have CNS involvement at diagnosis primary mediastinal lymphoma, intravascular large B-cell lymphoma, DLBCL leg-type, Burkitt lymphoma, high-grade lymphomas, double expressor lymphoma with active infection or other malignancy severe liver or kidney insufficiency allergy to any medication we plan to use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intravenous MTX<br>intravenous methotrexate at a dose of 1g/m2 for 4 courses | Drug: Methotrexate<br>* intravenous versus intrathecal methotrexate<br>|
| Experimental: intrathecal MTX<br>intrathecal methotrexate 10mg at a time for 4 courses | Drug: Methotrexate<br>* intravenous versus intrathecal methotrexate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 year CNS relapse rate | CNS relapse was defined as positive CSF conventionalcytology, CSF flow cytometry, or biopsy. For those who had clinical symptoms indicating a CNS involvement and typical lesions on MRI, the investigators also considered a recurrence | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | from diagnosis to any event including progression, relapse and death | 2 year | 
| overall survival | from diagnosis to death | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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central nervous system prophylaxis, methotrexate