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

Phase II Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat RA and RARS of MDS

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).

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Other: Human umbilical cord-derived MSCs; Other: cyclosporine A (CsA)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chengyun Zheng, PhD; Phone Number: +86-531-85875635; Email: chengyun.zheng@ki.se

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250033
      • Recruiting
      • Department of Hematology of the 2nd Hospital of Shandong University
      • Contact: Chengyun Zheng, PhD; Phone Number: +86-531-85875635; Email: chengyun.zheng@ki.se
      • Principal Investigator: chengyun zheng, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient age 18~80 years old with plan to infuse MSCs.
2. Histologically documented or cytologically confirmed diagnosis of MDS with WHO classification of MDS-RA and MDS-RARS.
3. Patients must have an ECOG 0~2.
4. No moderate or sever organ dysfunction: Ejection fraction>45%; Creatinine <176 mmol/L.
5. No active severe viral or fungus infection.
6. Each patient must sign written informed consent.

Exclusion Criteria:

1. Psychiatric condition that would limit informed consent.
2. HIV positive
3. Positive Pregnancy Test
4. Patient has enrolled another clinical trial study within last 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: cheng yun zheng, PhD, Department of Hematology of the 2nd Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): May 1, 2013

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 24, 2010
• First Posted (Estimate): May 25, 2010

Study Record Updates

• Last Update Posted (Estimate): May 25, 2010
• Last Update Submitted That Met QC Criteria: May 24, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Transplant; Bone Marrow Disease; MDS-RA; MDS-RARS; Umbilical Cord/placenta-Derived MSC
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CZheng; No. 30670903 (Other Identifier: National Natural Science Foundation of China)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No