MTX and Steroid as First-line Therapy for aGVHD

Study Overview
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Brief Summary
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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).

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 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.

Official Title
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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

Conditions
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Acute GVH 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 allogeneic hematopoietic stem cell transplantation; Patients with acute graft-versus-host disease of grade II-IV were diagnosed after transplantation; Patients with stable implantation of granulocytes and platelets. ECOG score ≤3 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

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>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<br>* MTX (5-10 mg/day,Dmax 10mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was CR<br>* Other names: Corticosteroid;|
| Active Comparator: corticosteroid<br>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<br>* corticosteroid Methylprednisolone 1 mg/kg/day was given for 10 days and then the dosage was gradually reduced according to patient's response<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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTX, acute GVHD, Corticosteroid