Safety and Efficacy Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat Severe Aplastic Anemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) derived from human umbilical cord/placenta at a dose of 1.0E+6 MSC/kg in subject for the therapy of severe aplastic anemia (SAA).

Detailed Description
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Severe aplastic anemia (SAA) is a condition that involves a low level of red blood cells, white blood cells, and platelets without evidence of another bone marrow disease. Patients with severe aplastic anemia produce too few blood cells, causing fatigue, easy bruising and bleeding, and susceptibility to infections. In many cases, the very low blood counts result from an autoimmune process. The patient's own immune system damages their stem cells in bone marrow. Although immune-suppressing drugs, such as corticosteroids, CsA and ATG, have been used in the treatment of SAA, however, many studies have indicated that the overall response rate to these drugs is less than 60%. Addition, the severe side effects of these immune-suppressing drugs have also been observed. The management of SAA patients therefore remains unsatisfactory and targeted therapies are needed. Human MSCs isolated from human umbilical cord/placenta have been shown to have immunosuppressive, stimulating hematopoiesis and tissue repairing properties. This study will evaluate the safety and effectiveness of MSC transplantation in the SAA patients. This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant and CsA therapy (experimental group) or CsA therapy alone (control group). Patients will undergo MSC transplant at the start of the study on Day 0. After 3 months, patients will receive the second MSC transplantation. After six and twelve months from the first transplantation, patients will be evaluated.

Official Title
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Phase II Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat SAA

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Other: Human umbilical cord-derived MSCs and cyclosporin A
* Other: cyclosporin A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age 18 80 years old with plan to infuse MSCs. Standard of diagnosis of aplastic anemia is according to Chinese domestic classification of AA for 1987. Patients must have an ECOG 0 2. No moderate or sever organ dysfunction: Ejection fraction>45%; Creatinine <176 umol/L. No active severe viral or fungus infection. Each patient must sign written informed consent. Exclusion Criteria: Psychiatric condition that would limit informed consent. HIV positive Positive Pregnancy Test Patient has enrolled another clinical trial study within last 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human umbilical cord-derived MSCs and cyclosporin<br>Human umbilical cord-derived MSCs at a dose of 1.0E+6 MSC/kg, repeated to apply in trimonthly for 2 cycle and CsA 5mg/kg po for 12 months | Other: Human umbilical cord-derived MSCs and cyclosporin A<br>* 1.0E+6 MSC/kg, IV drop and repeat to apply in trimonthly for 2 cycle and cyclosporin A 5mg/kg po for 12 months<br>|
| Active Comparator: cyclosporine A<br>cyclosporine A at a dose of 5 mg CsA/kg | Other: cyclosporin A<br>* cyclosporin A 5mg/kg po for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAA clinical symptoms | Anemia symptoms, bleeding and infection will be mainly observed in every monthly after transplanting MSCs for one year. | 1 year | 
| The number of blood cells | The number of blood cells, which contains WBC, Neu, RBC, Hb,PLT and reticulocyte, will be mainly tested monthly after transplantion of MSCs for one year | 1 year | 
| Bone borrow hemocytology | Bone borrow cytomorphologic examination will be tested in every 3 months after transplantion of MSCs for one year. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of systemic T regulatory cell population and T lymphocyte subsets | Percentages of T regulatory cell population and T lymphocyte subsets in peripheral blood will be tested in every 3 months after transplanting MSCs for one year. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Marrow Disease, Aplastic Anemia, Umbilical Cord/placenta-Derived MSC, Transplantation