Efficacy and Safety of UC-MSCs for the Treatment of Steroid-resistant aGVHD Following Allo-HSCT

Study Overview
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Brief Summary
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Randomized, open-label, multicenter study to investigate the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSC) for the treatment of steroid-resistant acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a view to establishing an effective treatment protocol for steroid-resistant aGVHD.

Detailed Description
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A total of 130 patients with steroid-resistant aGVHD after allo-HSCT are enrolled in this multicenter, randomized, controlled trial. Patients were randomized to UC-MSC + anti-CD25 monoclonal antibodies (mAb) group and anti-CD25 mAb group. The complete response (CR) rate after 4 weeks of treatment in the two groups will be compared. Adverse events are also recorded throughout the study.

Official Title
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Efficacy and Safety of UC-MSCS for the Treatment of Steroid-resistant aGVHD Following Allo-HSCT: A Multicenter, Randomized, Open-label Trial

Conditions
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Graft Vs Host Disease

Intervention / Treatment
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* Drug: UC-MSC
* Drug: Anti-CD25 mAb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Confirmed diagnosed steroid-resistant aGVHD after allo-HSCT. 2. Neutrophile granulocyte (ANC) ≥ 0.5 x 10^9/L. 3. Creatinine below 2 times normal upper limit . 4. Willing and able to sign written informed consent. Exclusion Criteria: - 1. Untoleratation of the treatment. 2. Primary disease are not effectively controlled or are progressing. 3. Active infection (Bacteria, fungi, viruses ). 4. Combined with dysfunction of multiple organ. 5. Female patients who are nursing or pregnant, or who contemplate pregnancy during the study period. 6. Patients who are deemed unsuitable for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: UC-MSC and anti-CD25 mAb<br>UC-MSC, iv, 1×10^6 cells/kg, once a week, for 4 weeks. Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, 4 weeks. Other treatment would replace it according to clinical experience if aGVHD continue to progress within 3 weeks of treatment or patients are lack of response after 4 weeks of treatment. The treatment would be repeated in another 4 weeks if patients receive partial response after the first 4 weeks of treatment. | Drug: UC-MSC<br>* UC-MSC, iv, 1×10^6 cells/kg, once a week, for 4 weeks.<br>* Other names: Umbilical cord-derived mesenchymal stem cells;Drug: Anti-CD25 mAb<br>* Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks.<br>* Other names: Basiliximab;|
| Active Comparator: Anti-CD25 mAb<br>Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks. Other treatment would replace it according to clinical experience if aGVHD continue to progress within 3 weeks of treatment or patients are lack of response after 4 weeks of treatment. The treatment would be repeated in another 4 weeks if patients receive partial response after first 4 weeks of treatment. | Drug: Anti-CD25 mAb<br>* Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks.<br>* Other names: Basiliximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete remission | Complete remission of aGVHD related symptoms and indicators | 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The time from randomization to death for any reason ( the last follow-up time for missing patients; end date of follow-up for patients who are live at the end of the study). | At the end of Week 4 / 8 / 12 / 24 / 52. | 
| Rate of partial remission | improvement of aGVHD staging in one or more organs without progression in other organs | 4 weeks after treatment | 
| Infusion toxicity | Acute toxicity responses include impaired function of heart, kidney and liver | From the beginning of to four hours after every infusion of UC-MSC |