MSCs Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant aGVHD

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of CD25 monoclonal antibody and calcineurin inhibitors with or without mesenchymal stem cells (MSCs) in treating patients with steroid-resistant acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for several hematological disorders. Although good progress has been made in the prevention and treatment of side effects associated with transplantation, aGVHDremains a common and life-threatening complication with poor prognosis. Corticosteroids are still acted as the first-line treatments of aGVHD, with a response rate of 50-80. However, those who failed to initial therapy only have 10-30% long-term survival. Mesenchymal stromal cells (MSCs) are a form of multipotent adult stem cells that can be isolated from many tissues, such as bone marrow (BM), adipose tissue and umbilical cord. Such cells possess the capacity to suppress immunological responses, support hematopoiesis and repair tissues. Clinical applications of human MSCs are evolving rapidly for preventing and treating GVHD. Although the results are still controversy, most prospective and retrospective data suggest that MSCs are effective to aGVHD. In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded BM-derived MSCs from third-party donors combined with CD25 monoclonal antibody and calcineurin inhibitors in treating patients with aGVHD.

Official Title
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Mesenchymal Stem Cells Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Conditions
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Acute Graft-versus-host Disease

Intervention / Treatment
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* Drug: CD25 monoclonal antibody
* Drug: calcineurin inhibitors
* Biological: MSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age of 14-65 years steroid-resistant aGVHD subjects (or their legally acceptable representatives) must have signed an informed consent document Exclusion Criteria: Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
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Minimum Age: 14 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: Mesenchymal stem cells<br>MSCs will be given at a median dose of 1×10^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used. | Drug: CD25 monoclonal antibody<br> <br> Drug: calcineurin inhibitors<br> <br> Biological: MSCs<br> <br> |
| Experimental: CD25 Mc Ab & calcineurin inhibitors<br>CD25 monoclonal antibody (20mg/kg, day 1,4,8,15,21) will be administered combined with calcineurin inhibitors. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. | Drug: CD25 monoclonal antibody<br> <br> Drug: calcineurin inhibitors<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of treatment for steroid-resistant aGVHD | The responses to aGVHD are according to the literature criteria, including completely response (CR), partial response (PR) and no response (NR), and CR is defined as resolution of all symptoms of aGVHD; PR is defined as a decrease by at least 1 GVHD stage in any 1 organ system without deterioration in others 24. Overall response (OR) includes CR and PR. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of infections | Infections are mainly focused on cytomegalovirus (CMV) and Epstein-Barr virus ( EBV) infections during study treatments and within one year after study treatments. | 1 year | 
| Incidence of primary underlying disease relapse |  | 1 year | 
| Incidence of chronic GVHD |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, CD25 Monoclonal Antibody, Acute Graft-versus-host disease