Safety and Efficacy Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat Myelodysplastic Syndromes

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 on the subjects for refractory anemia (RA) and refractory anemia with ring sideroblast (RARS) of myelodysplastic syndromes (MDS).

Detailed Description
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Myelodysplastic syndromes are bone marrow stem cell disorders resulting in disorderly and ineffective hematopoiesis. MDS is characterized by variable degrees of cytopenias (anemia, neutropenia, and thrombocytopenia ) and risk of transformation to leukemia. To date treatment of MDS is unsatisfactory: chemotherapy has a limited role in the management of leukemic progression; autologous stem cell transplantation does not prolong relapse-free survival and stem cell transplantation is poorly tolerated in older individuals. Some MDS patients have been shown to respond to a wide variety of immunosuppressive agents ranging from corticosteroids to CsA and antithymocyte globulin (ATG). However, the overall response rate is less than 30%. In fact, few treatments appear to change the natural history of MDS. The management of MDS patients therefore remains to be improved. Human MSCs isolated from Wharton's jelly of the 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 transplant in the MDS patients. This study will last about 3 years. Participants will be randomly assigned to receive either MSC transplant (Group 1) or CsA therapy alone (Group 2). Patients will undergo MSC transplant at the start of the study (defined as Day 0). After 3 months, patients will receive the second MSC transplantation when one responds well to the treatment. After 3, 6 and 12 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 RA and RARS of MDS

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Other: Human umbilical cord-derived MSCs
* Other: cyclosporine A (CsA)


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. Histologically documented or cytologically confirmed diagnosis of MDS with WHO classification of MDS-RA and MDS-RARS. Patients must have an ECOG 0 2. No moderate or sever organ dysfunction: Ejection fraction>45%; Creatinine <176 mmol/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<br>Human umbilical cord-derived MSCs at a dose of 1.0E+6 MSC/kg, repeated to apply in trimonthly for 2 cycle | Other: Human umbilical cord-derived MSCs<br>* 1.0E+6 MSC/kg, IV drop and repeat to apply in trimonthly for 2 cycle<br>|
| Active Comparator: cyclosporine A (CsA)<br>CsA at a dose of 5 mg CsA/kg | Other: cyclosporine A (CsA)<br>* CsA 5mg/kg po for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDS clinical symptoms (mainly anemia symptoms) | Anemia symptoms will be mainly observed in every week after transplanting MSCs for one year. | 1 year | 
| A routine blood test | A routine blood test, which contains WBC, Neu, RBC, Hb and PLT, will be mainly tested in every month after transplanting MSCs for one year. | 1 year | 
| Bone borrow cytomorphologic examination | Bone borrow cytomorphologic examination will be tested in every 3 months after transplanting MSCs for one year. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of T regulatory cell population in peripheral blood | Percentage of T regulatory cell population 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, MDS-RA, MDS-RARS, Umbilical Cord/placenta-Derived MSC, Transplant