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

NCT ID: NCT05054426

Last Updated: 2021-09-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 488 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-08
• Study Completion Date: 2025-10-08

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.

Conditions

Diffuse Large B Cell Lymphoma; Central Nervous System Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intravenous MTX

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

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

intravenous versus intrathecal methotrexate

intrathecal MTX

intrathecal methotrexate 10mg at a time for 4 courses

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

intravenous versus intrathecal methotrexate

Interventions

Methotrexate

intravenous versus intrathecal methotrexate

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

YanZhang

associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daobin Zhou, MD.

Role: STUDY_CHAIR

Peking Union Medical College Hospital

Locations

Peking union medical college hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Wang, MD.

Role: CONTACT

wangweipumc@163.com

8613810131294

Daobin Zhou, MD.

Role: CONTACT

zhoudb@pumch.cn

8613901113623

Facility Contacts

Daobin Zhou, MD.

Role: primary

8613901113623

References

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.

Reference Type: RESULT

PMID: 31925808 (View on PubMed)

Other Identifiers

PUMCH-NHL-011

Identifier Type: -

Identifier Source: org_study_id