MSC for Treatment of cGVHD After Allo-HSCT

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of mesenchymal stem cells in patients with chronic graft-versus-host disease.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation(allo-HSCT) can cure many hematologic diseases. Although great progress has been made in the prevention and treatment of side effects associated with transplantation,chronic graft-versus-host disease(cGVHD) remains an important complication that occurs in about 50% patients. The mortality of cGVHD and its complication could reach up to 50%,and cGVHD seriously influence the quality of life. At present, the first line treatment of cGVHD remains in discussion. Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs are evolving rapidly with goals of improving hematopoietic engraftment, preventing and treating GVHD after allo-HSCT and so on. However, the efficacy of treatment of cGVHD remains undetermined. In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded MSCs in treating patients with cGVHD.

Official Title
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Mesenchymal Stem Cell for Treatment of Chronic Graft-versus-host Disease After Allogenetic Hematopoietic Stem Cell Transplantation

Conditions
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Chronic Graft-versus-host Disease

Intervention / Treatment
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* Biological: Mesenchymal stem cells
* Drug: Glucocorticoids
* Drug: cyclosporine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient age of 18-65 years Recipients of allogeneic hematopoietic stem cell transplantation Patients with moderate/ severe cGVHD without systemic treatment Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Primary disease relapse Expected lifetime less than 3 months Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
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Minimum Age: 18 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: MSCs group<br>MSCs group refers to treatment with mesenchymal stem cells (1×10^6 cells/kg, intravenously) weekly for 8 doses. Besides, glucocorticoids and cyclosporine (CsA) will be used for treatment concurrently. | Biological: Mesenchymal stem cells<br>* Mesenchymal stem cells (MSCs) will be intravenously infused via a central venous catheter(at a dose of 1×10^6 cells/kg, over 15 mins) weekly. MSCs will be administrated for 8 doses.<br>Drug: Glucocorticoids<br>* Glucocorticoids (i.e. Methylprednisolone) will be used with an initial dose of 1mg/kg.<br>Drug: cyclosporine<br>* Cyclosporine (CsA) will be used with an initial dose of 2.5mg/kg/d and adjusted according to the concentration of CsA. The targeted concentration is 200-300 ng/Ml.<br>|
| Active Comparator: Control group<br>Glucocorticoids and CsA will be used for treatment. | Drug: Glucocorticoids<br>* Glucocorticoids (i.e. Methylprednisolone) will be used with an initial dose of 1mg/kg.<br>Drug: cyclosporine<br>* Cyclosporine (CsA) will be used with an initial dose of 2.5mg/kg/d and adjusted according to the concentration of CsA. The targeted concentration is 200-300 ng/Ml.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall response rate （ORR）includes complete response (CR) and part response (PR). | 12 weeks after the first dose of MSCs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival (OS) | 1 year after the first dose of MSCs | 
| DFS | Disease-free survival (DFS) | 1 year after the first dose of MSCs | 
| Response rate |  | 4 weeks after the first dose of MSCs | 
| EBV DNA-emia | EBV DNA-emia refers to detection of EBV DNA in peripheral blood via PCR. | 1 year after the first dose of MSCs | 
| CMV DNA-emia | CMV DNA-emia refers to detection of CMV DNA in peripheral blood via PCR. | 1 year after the first dose of MSCs | 
| PGF | Poor graft function (PGF) refers to a slow or incomplete recovery of blood cell counts (ANC ≤0.5x10^9/L and PLT ≤20x10^9/L) by +28 days after allo-HSCT or a fall in blood cell counts to levels fulfilling the diagnostic criteria for PGF after successful and prompt hematopoietic engraftment. | 1 year after the first dose of MSCs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cell Transplantation, Chronic Graft-versus-host disease, Mesenchymal Stem Cells