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

Diffuse Large B Cell Lymphoma Clinical Trial

— NHL-011  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05054426
• Other study ID #: PUMCH-NHL-011
• Status: Recruiting
• Phase: Phase 3
• Start date: October 8, 2021
• Est. completion date: October 8, 2025

Study information

• Verified date: September 2021
• Source: Peking Union Medical College Hospital
• Contact: Wei Wang, MD.
• Phone: 8613810131294
• Email: wangweipumc[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 488
• Est. completion date: October 8, 2025
• Est. primary completion date: October 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Central Nervous System Lymphoma
• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Methotrexate
intravenous versus intrathecal methotrexate

Locations

Country	Name	City	State
China	Peking union medical college hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

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/m(2) incorporated into RCHOP prevented CNS relapse in high-risk DLBCL patients: A prospective, histor — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	progression free survival	from diagnosis to any event including progression, relapse and death	2 year
Secondary	overall survival	from diagnosis to death	2 year