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

Phase 3

Recruiting

• Conditions: Diffuse Large B Cell Lymphoma; Central Nervous System Lymphoma
• Interventions: Drug: Methotrexate

• Registration Number: NCT05054426
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-09
• Study First Submitted: 2021-09-01
• Study First Submitted QC: 2021-09-21
• Last Update Submitted: 2021-09-21
• Study First Posted: 2021-09-23
• Last Update Posted: 2021-09-23
• Study Start: 2021-10-08
• Primary Completion: 2025-10-08
• Study Completion: 2025-10-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 488

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
intravenous MTX	Methotrexate	intravenous methotrexate at a dose of 1g/m2 for 4 courses
intrathecal MTX	Methotrexate	intrathecal methotrexate 10mg at a time for 4 courses

Primary Outcome Measures

Name	Time	Method
2 year CNS relapse rate	2 year	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

Secondary Outcome Measures

Name	Time	Method
progression free survival	2 year	from diagnosis to any event including progression, relapse and death
overall survival	2 year	from diagnosis to death

Trial Locations

Locations (1)

Peking union medical college hospital; 🇨🇳 Beijing, Beijing, China