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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Graft Versus Host Disease

Intervention / Treatment
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* Drug: MTX
* Drug: Corticosteroid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are fully informed and sign informed consent by themselves or their guardians; Patients receiving first allogeneic hematopoietic stem cell transplantation; Patients with acute graft-versus-host disease of grade II-IV were diagnosed after transplantation; KPS>60, Estimated survival >3 months; No serious organ damage: ANC in peripheral blood is greater than 0.5×109/l Creatinine < 1.5mg/dl Cardiac ejection index > 55% Exclusion Criteria: Patients with severe brain, heart, kidney or liver dysfunction unrelated to graft-versus host disease; Patients with uncontrollable active infection; Patients with recurrence of primary malignant hematopathy; Expected survival is less than 3 months Patients who have histories of severe allergic reactions Pregnant or lactating women The researcher judges that there are other factors that are not suitable for participating Patients who received donor lymphocyte infusion

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTX and corticosteroid<br>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<br>* MTX (5mg/m^2/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR<br>|
| Active Comparator: Corticosteroid<br>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<br>* 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).<br>|

What is the study measuring?
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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 |