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

Phase 3

Recruiting

• Conditions: Acute Graft Versus Host Disease
• Interventions: Drug: Corticosteroid; Drug: MTX

• Registration Number: NCT05921305
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-06-19
• Study First Submitted QC: 2023-06-19
• Study First Posted: 2023-06-27
• Study Start: 2023-08-03
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-07
• Last Update Posted: 2023-10-10
• Primary Completion: 2024-06-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 218

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
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).
MTX and corticosteroid	MTX	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.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) for aGVHD treatment after treatment	14 days	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

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) for aGVHD treatment at 28 days after treatment	28 days	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
Overall response rate (ORR) for aGVHD treatment at 42 days after treatment	42 days	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
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	42 days	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.
cGVHD	1 years	The cumulative incidence of chronic GVHD
Infection and poor graft function	1 year	The cumulative incidence of severe infection and poor graft function
Relapse	1 year	The cumulative incidence of relapse
Non-relapse mortality	1 year	The cumulative incidence of non-relapse mortality
Overall survival	1 year	The cumulative incidence of overall survival
Disease free survival	1 year	The cumulative incidence of disease free survival

Trial Locations

Locations (2)

Nanfang Hospital, Nanfang Medical University; 🇨🇳 Guangzhou, Guangdong, China

Peking University Institute of Hematology,; 🇨🇳 Beijing, Beijing, China