Mesenchymal Stem Cells Transplantation for Refractory Systemic Lupus Erythematosus (SLE)

Refractory Systemic Lupus Erythematosus Clinical Trial

Official title:

Phase I/IIa: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells Transplantation For Refractory Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00698191
• Other study ID #: NSFC30772014
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: June 13, 2008
• Last updated: June 16, 2008
• Start date: March 2007
• Est. completion date: December 2012

Study information

• Verified date: June 2008
• Source: Nanjing Medical University
• Contact: Sun Lingyun, MD
• Phone: +86 25 83105219
• Email: lingyunsun2001[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will explore a new approach to treat patients with a medical condition known as systemic lupus erythematosus (SLE) who have been resistant to previous treatments using a new population of cells with capability to restore a normal immune system that will no longer attack the body.

The stated hypothesis is that the SLE condition is caused by an abnormal immune system that can be restored by replenishing the body with a new population of progenitor cells.

Description:

The purpose of this study is to evaluate the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell (AlloMSC) transplantation in patients with refractory SLE. Patients with Lupus nephritis and refractory to corticosteroid or cyclophosphamide trials will be enrolled in this trial. The treatment intervention includes a 24 hour pretreatment with cyclophosphamide followed by AlloMSC transplantation. Patients will be admitted to the in-patient service for the 3-5 days for the transplant treatment and will be followed up in the outpatient clinic. All baseline lupus serology, renal function panels will be obtained at pre-treatment admission. Post-transplantation follow-up visits will be at monthly intervals for lupus serology and renal function tests, and every 3 months for analysis of T regulatory population. The transplanted patients will be evaluated by an integrated team of rheumatologists, hematologists and bone marrow transplant specialists every month for the entire duration of the trial (2 years) and every 6-12 months thereafter.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 70 Years

Eligibility

Inclusion Criteria:

• All patients fulfilled the American College of Rheumatology (ACR) criteria of SLE, man or woman aged from 15 to 70 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 MMF 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 mos 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;

• Undercontrolled infections

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Refractory Systemic Lupus Erythematosus

Intervention

Biological:
• Allogeneic MSC (AlloMSC)
Intervention: Cyclophosphamide will be administered intravenously at at total dose of 0.8-1.8g 24 hours before transplantation. Allogeneic bone marrow derived mesenchymal stem cells (matched family donors)will be infused intravenously at 106 cells/kg body weight

Locations

Country	Name	City	State
China	Department of Rheumatology and Immunology, Nanjing University Medical College Affiliated Drum Tower Hospital	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Nanjing Medical University	National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

References & Publications (3)

Jiang B, Sun L, Hao S, Li X, Hou Y. Estrogen distinctively modulates spleen DC from (NZB x NZW) F1 female mice in various disease development stages. Cell Immunol. 2007 Aug;248(2):95-102. Epub 2007 Dec 3. — View Citation

Jiang B, Sun L, Hao S, Li X, Xu Y, Hou Y. Estrogen modulates bone marrow-derived DCs in SLE murine model-(NZB x NZW) F1 female mice. Immunol Invest. 2008;37(3):227-43. doi: 10.1080/08820130801973328. — View Citation

Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW, Fan LM. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007;16(2):121-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)		Monthly	Yes
Primary	Lupus serology (ANA, dsDNA, C3, C4)		Monthly	Yes
Primary	Renal function (GFR, BUN, urinalysis)		Monthly	Yes
Secondary	Percentage of systemic T regulatory population		Every 3 months	No