Mini-dose MTX Plus Standard-dose Steroid for the Initial Treatment of Acute GVHD

Randomized Trial of Mini-dose Methotrexate Plus Standard-dose Steroid vs Steroids for the Initial Treatment of Acute Graft Versus Host Disease

This trial is a randomized (1:1) phase III open label study of frontline mini-MTX plus methylprednisolone 2mg/kg/day compared to methylprednisolone 2mg/kg in allogeneic stem cell transplant recipients with grade 2-4 aGVHD.

Study Overview

• Status: Recruiting
• Conditions: Acute Graft Versus Host 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. Corticosteroid is the standard first-line therapy for aGVHD. 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 control aGVHD.

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yu Wang, M.D.; Phone Number: 86-13552647384; Email: ywyw3172@sina.com
• Study Contact Backup: Name: Xiao-Jun Huang, M.D.

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Institute of Hematology,
      • Contact: Yu Wang, Dr.; Phone Number: 13552647384; Email: ywyw3172@sina.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital, Nanfang Medical University
      • Contact: qifa liu, M.D.; Email: liuqifa628@163.com
      • Principal Investigator: qifa liu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 first allogeneic hematopoietic stem cell transplantation;
3. Patients with acute graft-versus-host disease of grade II-IV were diagnosed after transplantation;
4. KPS>60, Estimated survival >3 months;

5. No serious organ damage:

   1. ANC in peripheral blood is greater than 0.5×109/l
   2. Creatinine < 1.5mg/dl
   3. Cardiac ejection index > 55%

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
8. Patients who received donor lymphocyte infusion

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; Methylprednisolone 2 mg/kg/day was given for 3 days, and for responding patients, the dose of prednisone must be at least 0.25mg/kg/day prednisone (or 0.2mg/kg/day methylprednisolone). MTX (5mg/m^2/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR.	Drug: MTX; MTX (5mg/m^2/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR
Active Comparator: Corticosteroid; Methylprednisolone 2 mg/kg/day was given for 3 days, and for responding patients, the dose of prednisone must be at least 0.25mg/kg/day prednisone (or 0.2mg/kg/day methylprednisolone).	Drug: Corticosteroid; Corticosteroid Methylprednisolone 2 mg/kg/day was given for 3 days, and for responding patients, the dose of prednisone must be at least 0.25mg/kg/day prednisone (or 0.2mg/kg/day methylprednisolone).

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	14 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

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: June 19, 2023
• First Submitted That Met QC Criteria: June 19, 2023
• First Posted (Actual): June 27, 2023

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

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: GVHD-MTX-Randomized trial

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