Multicenter Clinical Trial for the Evaluation of Mesenchymal Stem Cells From Adipose Tissue in Patients With Chronic Graft Versus Host Disease.

Study Overview
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Brief Summary
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The main purpose of this trial is to assess the safety and feasibility of treatment with two-dose infusion of allogeneic mesenchymal stem cells from adipose tissue expanded in vitro in patients undergoing haematopoietic stem cell transplantation (HSCT, who have developed chronic and extensive graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) express low levels of HLA class I molecules, and do not express class II molecules neither CD40, CD80 and CD86, being unable to induce proliferation of allogeneic lymphocytes. In addition, MSCs inhibit lymphocyte proliferation by inhibiting cell division and maintaining these cells in a quiescent state. This supports the hypothesis that MSCs are universal suppressors.

Official Title
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Multicenter Clinical Trial Phase I/II Randomized, Controlled, for the Evaluation of Safety and Feasibility of Therapy With Two Different Doses of Allogenic Mesenchymal Stem Cells From Adipose Tissue in Patients With Chronic Graft Versus Host Disease.

Conditions
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Graft Versus Host Disease, Chronic and Expanded Graft Versus Host Disease, Immune System Diseases

Intervention / Treatment
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* Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.
* Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who develop chronic extensive GVHD as determined by the National Institute of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD (Biol Blood Marrow Transplant 2005; 11: 945-955), and which meet the following criteria: They have never received therapy for chronic GVHD. They have de novo or quiescent chronic extended GVHD. Exclusion Criteria: Concomitant severe systemic infection. Oncologic or hematological condition relapse. Pregnancy. Estimated life expectancy less than 1 week. Patients who do not give their informed consent.

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: Conventional treatment plus high dose: 3x10e6 cells / Kg.<br>Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin. | Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.<br>* Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. Low dose: 1 x10e6 / Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.<br>Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.<br>* Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. High dose: 3 x10e6/Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.<br>|
| Experimental: Conventional treatment plus low dose: 1x10e6 cells / Kg<br>Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin. | Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.<br>* Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. Low dose: 1 x10e6 / Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.<br>Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.<br>* Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. High dose: 3 x10e6/Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients in each group that may potentially reduce corticosteroids at week 7, 20 and 42, started immunosuppressive treatment and percentage of patients at week 56 have been suspended on full immunosuppressive treatment |  | 12 months | 
| Overall survival and disease-free survival. |  | 12 months | 
| Changes in lymphocyte subsets and levels of inflammatory and antiinflammatory cytokines in each of the groups. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft versus host disease, Mesenchymal stem cell, Allogeneic mesenchymal stem cell, Adipose tissue, Allotransplant, Allogenic, Mesenchymal Stem Cells, Immune System Diseases, Chronic, Expanded