Umbilical Cord Derived Mesenchymal Stem Cells Transplantation for Active and Refractory Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

Phase I/II: Umbilical Cord Derived Mesenchymal Stem Cells Transplantation For Active And Refractory Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01741857
• Other study ID #: NJGLYY005
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: November 26, 2012
• Last updated: November 1, 2013
• Start date: January 2012
• Est. completion date: December 2013

Study information

• Verified date: October 2012
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will explore safety and efficacy of allogeneic umbilical cord (UC) derived mesenchymal stem cells transplantation (MSCT) to treat patients with active and refractory systemic lupus erythematosus (SLE) who have been resistant to multiple standard treatments. The underlying hypothesis is that the active SLE condition is caused by an abnormal immune homeostasis that can be restored by MSCT.

Description:

Inclusion Criteria:

1. All patients fulfilled the American College of Rheumatology (ACR) criteria of SLE, man or woman aged from 15 to 70 years old, SLEDAI≥8;

2. Lupus nephritis with 24h urine protein≥1g;

3. Refractory disease as determined by failure of the following regimens:

Trial of corticosteroids (oral prednisone more than 20 mg/day); Trial of cyclophosphamide 0.4 ~ 0.6 / m2 every two weeks for six months, or other immunosuppressive drugs, such as mycophenolate mofetil 2 g / day, for three months;

4. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital;

5. Willing to use contraception throughout the study and for 12 months following treatment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 60 Years

Eligibility

Inclusion Criteria:

• All patients fulfilled the American College of Rheumatology (ACR) criteria of SLE, man or woman aged from 15 to 60 years old, SLEDAI=8;

• Lupus nephritis with 24h urine protein=1g;

• Refractory disease as determined by failure of the following regimens:

Trial of corticosteroids (oral prednisone more than 20 mg/day); Trial of cyclophosphamide 0.4 ~ 0.6 / m2 every two weeks for six months, or other immunosuppressive drugs, such as mycophenolate mofetil 2 g / day, for three months;

• Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital;

• Willing to use contraception throughout the study and for 12 months following treatment

Exclusion Criteria:

• Abnormal liver function (ALT higher than 3 times the normal value);

• End-stage renal failure;

• Severe heart and pulmonary failure, or other important organs damage;

• Uncontrolled infections

• Pregnant or breast feeding women, male or female who intended to recent pregnancy

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• human umbilical cord derived MSC transplantation for SLE

Locations

Country	Name	City	State
China	The Affiliated Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

References & Publications (8)

Che N, Li X, Zhou S, Liu R, Shi D, Lu L, Sun L. Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation. Cell Immunol. 2012;274(1-2):46-53. doi: 10.1016/j.cellimm.2012.02.004. Epub 2012 Feb 23. — View Citation

Liang J, Gu F, Wang H, Hua B, Hou Y, Shi S, Lu L, Sun L. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol. 2010 Aug;6(8):486-9. doi: 10.1038/nrrheum.2010.80. Epub 2010 Jun 1. — View Citation

Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463. Erratum in: Ann Rheum Dis. 2011 Jan;70(1):237. — View Citation

Shi D, Wang D, Li X, Zhang H, Che N, Lu Z, Sun L. Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clin Rheumatol. 2012 May;31(5):841-6. doi: 10.1007/s10067-012-1943-2. — View Citation

Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, Xu T, Le A, Shi S. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009 Jun;27(6):1421-32. doi: 10.1002/stem.68. — View Citation

Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010 Aug;62(8):2467-75. doi: 10.1002/art.27548. — View Citation

Wang D, Akiyama K, Zhang H, Yamaza T, Li X, Feng X, Wang H, Hua B, Liu B, Xu H, Chen W, Shi S, Sun L. Double allogenic mesenchymal stem cells transplantations could not enhance therapeutic effect compared with single transplantation in systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:273291. doi: 10.1155/2012/273291. Epub 2012 Jul 9. — View Citation

Zhang H, Zeng X, Sun L. Allogenic bone-marrow-derived mesenchymal stem cells transplantation as a novel therapy for systemic lupus erythematosus. Expert Opin Biol Ther. 2010 May;10(5):701-9. doi: 10.1517/14712591003769816. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	British Isles Lupus Assessment Group score (BILAG)		up to 12 months	Yes
Secondary	Lupus serology (Alb, ANA, dsDNA, C3, C4)		pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation	Yes
Secondary	Renal function (GFR, Blood Urea Nitrogen, urinalysis)		pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation (for GFR assessed at baseline and 12 months after MSCT)	Yes