Clinical trial NCT01741857: Umbilical Cord Derived Mesenchymal Stem Cells Transplantation for Active and Refractory Systemic Lupus Erythematosus
Official title: Phase I/II: Umbilical Cord Derived Mesenchymal Stem Cells Transplantation For Active And Refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2012-12-05
Enrollment: 40
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: British Isles Lupus Assessment Group score (BILAG)
timeFrame: up to 12 months
Secondary outcomes:
measure: Lupus serology (Alb, ANA, dsDNA, C3, C4)
timeFrame: pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation
measure: Renal function (GFR, Blood Urea Nitrogen, urinalysis)
timeFrame: pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation (for GFR assessed at baseline and 12 months after MSCT)
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The Affiliated Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Lingyun Sun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
citation: 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.
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.
citation: Wang D, Feng X, Lu L, Konkel JE, Zhang H, Chen Z, Li X, Gao X, Lu L, Shi S, Chen W, Sun L. A CD8 T cell/indoleamine 2,3-dioxygenase axis is required for mesenchymal stem cell suppression of human systemic lupus erythematosus. Arthritis Rheumatol. 2014 Aug;66(8):2234-45. doi: 10.1002/art.38674.
citation: Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, Hu X, Jiang S, Shi S, Sun L. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther. 2014 Mar 25;16(2):R79. doi: 10.1186/ar4520.