Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Chronic Graft Versus Host Disease

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) for the treatment of patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to first-line therapy. The secondary purpose of the study is to evaluate the effect of mesenchymal stem cells (MSC) on one-year survival rate, long-term survival rate, life quality and recurrence of patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to hormone treatment.

Detailed Description
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Chronic Graft-versus-host disease (GVHD)， with the incidence of 30%-60%, is a serious late complication of allogeneic hematopoietic stem cell transplantation (HSCT) and is the major cause of death in the late stage of transplantation. According to targeted organs, cGVHD is divided into two types, limited cGVHD and extensive cGVHD. Extensive cGVHD needs systemic immunosuppressant treatment. However, currently standard first-line regimen including cyclophosphamide and prednisolone is only effective for some patients. Novel treatment is urgently needed. Our previous study has shown that mesenchymal stem cells (MSCs) are effective for cGVHD patients with multiple skin damage. To further explore the therapeutic effect of MSCs for extensive cGVHD, we plan to conduct a multi-center clinical trial. Patients who developed an extensive cGVHD (with skin and/or liver damage) after HSCs transplantation and do not respond to first-line therapy are enrolled. They will be randomly divided into two groups which will receive MSCs and routine second-line drugs respectively. We will evaluate the efficacy and safety of MSCs for extensive cGVHD by comparison of symptom improvement, survival rate, recurrence as well as side effects in the two groups.

Official Title
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Phase Ⅱ/Ⅲ Clinical Trial, Multicenter, Randomized, Controlled, for the Evaluation of Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells in Patients With Chronic Graft Versus Host Disease

Conditions
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Chronic Graft Versus Host Disease

Intervention / Treatment
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* Biological: Biological: mesenchymal stem cell
* Drug: Cyclosporine and Glucocorticoid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Extensive cGVHD with skin and/or liver damage developed after allogeneic hematopoietic stem cell transplantation cGVHD that do not response to conventional immunosuppressant treatment for two months KPS>= 30 informed consent from the patient Exclusion Criteria: Extensive cGVHD without skin or liver damage With other acute severe complications In pregnancy or lactation Disease relapses With non-hematological malignancy Have a history of mental disorder, drug or alcohol abuse over the past five years Allergic Participate in other clinical trial within three months before the start of this trial With bone marrow fibrosis Have undergone hematopoietic stem cell transplantation to treat solid tumor

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 60 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: allogenic mesenchymal stem cells (MSCs)<br>patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to standard first-line regimen including cyclophosphamide and prednisolone. | Biological: Biological: mesenchymal stem cell<br>* Mesenchymal stem cells, 1-2×107, bone marrow injection, once a week for the first four weeks; whether to continue after four weeks depends on patients' symptoms.<br>* Other names: Regenerative medicine: MSCs;|
| Active Comparator: Control group<br>patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to standard first-line regimen including cyclophosphamide and prednisolone. | Drug: Cyclosporine and Glucocorticoid<br>* Calmodulin inhibitors such as cyclosporine, combined with Glucocorticoid 0.5-1mg/kg/d ,to the end of the study.<br>* Other names: Calmodulin inhibitors combined with Glucocorticoid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The total Response rate defined as patients with complete and partial response |  | 1 year after MSCs administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| one-year survival rate |  | 1 year after MSCs administration | 
| disease relapse |  | 2 years after MSCs administration | 
| quality of life |  | 2 years after MSCs administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cGVHD