MTX and Steroid as First-line Therapy for aGVHD

A Multi-cohort, Phase Ⅲ Study of Methotrexate Combined Corticosteroid as First-line Therapy in Chinese Patients With Acute Graft vs. Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

The aim of the study is to identify the efficacy and safety of methotrexate (MTX) combined corticosteroid as first-line therapy for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT).

Study Overview

• Status: Completed
• Conditions: Acute GVH Disease
• Intervention / Treatment: Drug: MTX; Drug: Corticosteroid

Detailed Description

Allo-HSCT is an effective treatment of malignant hematopoietic diseases. However, aGVHD remains a major complication after allo-HSCT and the destruction of recipient tissues by alloantigen-activated T cells is a key event in the development of aGVHD. Corticosteroid is the standard first-line therapy for aGVHD due to their roles in suppressing T cell responses. However, the response rate of corticosteroid was approximate 50%, and the clinical outcomes of patients with corticosteroid refractory GVHD were poor. Thus far, no combination therapy had been prove to be superior to corticosteroid alone as initial therapy for aGVHD. The study hypothesis: MTX combined corticosteroid treatment could help to further ameliorate the activity of T cells and control aGVHD.

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who are fully informed and sign informed consent by themselves or their guardians;
2. Patients receiving allogeneic hematopoietic stem cell transplantation;
3. Patients with acute graft-versus-host disease of grade II-IV were diagnosed after transplantation;
4. Patients with stable implantation of granulocytes and platelets.
5. ECOG score ≤3

Exclusion Criteria:

1. Patients with severe brain, heart, kidney or liver dysfunction unrelated to graft-versus host disease;
2. Patients with uncontrollable active infection;
3. Patients with recurrence of primary malignant hematopathy;
4. Expected survival is less than 3 months
5. Patients who have histories of severe allergic reactions
6. Pregnant or lactating women
7. The researcher judges that there are other factors that are not suitable for participating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MTX and corticosteroid; perimental: MTX and corticosteroid Methylprednisolone 1 mg/kg/day was given for 10 days and then gradually reduce the dose according to patient's response MTX (5-6mg/m^2/day,Maximum dose 10mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR	Drug: MTX; MTX (5-10 mg/day,Dmax 10mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR; Other Names: Corticosteroid
Active Comparator: corticosteroid; perimental: corticosteroid Methylprednisolone 1 mg/kg/day was given for 10 days and then gradually reduce the dose according to patient's response	Drug: Corticosteroid; corticosteroid Methylprednisolone 1 mg/kg/day was given for 10 days and then the dosage was gradually reduced according to patient's response

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) for aGVHD treatment after treatment	Overall response rate is defined as the proportion of patients demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) for aGVHD treatment at 28 days after treatment	Overall response rate is defined as the proportion of patients demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response	28 days
Overall response rate (ORR) for aGVHD treatment at 42 days after treatment	Overall response rate is defined as the proportion of patients demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response	42 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Data collection including questionnaires at individual and group visits and physician interviews at individual visits will be used to assess participants for treatment-related adverse events.	42 days
cGVHD	The cumulative incidence of chronic GVHD	1 years
Infection and poor graft function	The cumulative incidence of severe infection and poor graft function	1 year
Relapse	The cumulative incidence of relapse	1 year
Non-relapse mortality	The cumulative incidence of non-relapse mortality	1 year
Overall survival	The cumulative incidence of overall survival	1 year
Disease free survival	The cumulative incidence of disease free survival	1 year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiao-Jun Huang, Dr., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2021
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 14, 2021

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Corticosteroid; MTX; acute GVHD
• Other Study ID Numbers: NFEC-202105-K3-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No