Intermediate Dose of IV MTX as CNS Prophylaxis for High Risk DLBCL (NHL-011)

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 3

Conditions: Central Nervous System Lymphoma; Diffuse Large B Cell Lymphoma

Treatments: Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT05054426

PUMCH-NHL-011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 488 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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488 participants in 2 patient groups

intravenous MTX

Experimental group

Description:

intravenous methotrexate at a dose of 1g/m2 for 4 courses

Treatment:

Drug: Methotrexate

intrathecal MTX

Experimental group

Description:

intrathecal methotrexate 10mg at a time for 4 courses

Treatment:

Drug: Methotrexate