Clinical trial NCT05054426: Intermediate Dose of IV MTX as CNS Prophylaxis for High Risk DLBCL
Official title: Intravenous Methotrexate 1g/m2 as Central Nervous System Prophylaxis for High Risk Diffuse Large B Cell Lymphoma: a Prospective, Phase III, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B Cell Lymphoma
Central Nervous System Lymphoma
Keywords: central nervous system prophylaxis
methotrexate
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-09-23
Enrollment: 488
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 2 year CNS relapse rate
timeFrame: 2 year
Secondary outcomes:
measure: progression free survival
timeFrame: 2 year
measure: overall survival
timeFrame: 2 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou, MD.
role: STUDY_CHAIR
References:
citation: Wang W, Zhang Y, Zhang L, Yang C, Feng J, Cai H, Chen M, Cao X, Zhuang J, Zhu T, Duan M, Zhang W, Li J, Zhou D. Intravenous methotrexate at a dose of 1 g/m2 incorporated into RCHOP prevented CNS relapse in high-risk DLBCL patients: A prospective, historic controlled study. Am J Hematol. 2020 Apr;95(4):E80-E83. doi: 10.1002/ajh.25723. Epub 2020 Jan 22. No abstract available.