MTX and Steroid for III-IV aGVHD Treatment

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 treatment for grade III-IV acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

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 Single-cohort, Phase II Study of Methotrexate Combined Corticosteroid in Chinese Patients With Grade III-IV Acute Graft vs. Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Acute Graft Versus Host Disease

Intervention / Treatment
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* Drug: Methotrexate


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 III-IV were diagnosed after transplantation; Patients with stable implantation of granulocytes and platelets. Exclusion Criteria: Patients who have received more than one transplant; Patients with overlap syndrome; Patients within six months after the failure of the first transplantation; Patients with uncontrollable active infection; Patients with recurrence of primary malignant hematopathy; Patients with donor lymphocyte infusion induced graft-versus-host disease after first intervention; Patients with serious respiratory diseases; Patients with severe renal insufficiency; Patients with serious and uncontrolled heart disease; Patients with severe hepatobiliary diseases unrelated to graft-versus host disease; Within one week patients who need to use more than 1mg/kg/d methylprednisolone for reasons other than graft-versus-host disease; patients who have participated in other clinical trials within 1 month; 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTX and corticosteroid<br>Methylprednisolone 2 mg/kg/day MTX (5-10 mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II | Drug: Methotrexate<br>* Methylprednisolone 2 mg/kg/day MTX (5-10 mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II<br>* Other names: Corticosteroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) for GVHD 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) 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 | 
| relapse rate | Relapse rate is defined as the proportion of patients demonstrating a morphological relapse of the original malignant hematological disease | 1 year | 
| Non-relapse mortality | Non-relapse mortality | 1 year | 
| Overall survival | Overall survival | 1 year | 
| Disease free survival | Disease free survival | 1 year | 
| Failure free survival | Failure free survival | 1 year | 
| Chronic GVHD | number of participants with chronic GVHD at one year | 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