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

Primary Purpose

Diffuse Large B Cell Lymphoma, Central Nervous System Lymphoma

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Methotrexate

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring central nervous system prophylaxis, methotrexate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Peking union medical college hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

intravenous MTX

intrathecal MTX

Arm Description

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

intrathecal methotrexate 10mg at a time for 4 courses

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

progression free survival

from diagnosis to any event including progression, relapse and death

overall survival

from diagnosis to death

Full Information

NCT ID

NCT05054426

First Posted

September 1, 2021

Last Updated

September 21, 2021

Sponsor

Peking Union Medical College Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05054426

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Recruiting

Study Start Date

October 8, 2021 (Anticipated)

Primary Completion Date

October 8, 2025 (Anticipated)

Study Completion Date

October 8, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B Cell Lymphoma, Central Nervous System Lymphoma

Keywords

central nervous system prophylaxis, methotrexate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

488 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

intravenous MTX

Arm Type

Experimental

Arm Description

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

Arm Title

intrathecal MTX

Arm Type

Experimental

Arm Description

intrathecal methotrexate 10mg at a time for 4 courses

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

intravenous versus intrathecal methotrexate

Primary Outcome Measure Information:

Title

2 year CNS relapse rate

Description

Time Frame

2 year

Secondary Outcome Measure Information:

Title

progression free survival

Description

from diagnosis to any event including progression, relapse and death

Time Frame

2 year

Title

overall survival

Description

from diagnosis to death

Time Frame

2 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wei Wang, MD.

Phone

8613810131294

wangweipumc@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Daobin Zhou, MD.

Phone

8613901113623

zhoudb@pumch.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daobin Zhou, MD.

Organizational Affiliation

Peking Union Medical College Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Peking union medical college hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100005

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daobin Zhou, MD.

Phone

8613901113623

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31925808

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.

Results Reference

result

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

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