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

NCT ID: NCT00698191

Last Updated: 2008-06-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2012-12-31

Brief 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.

Detailed 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.

Conditions

Refractory Systemic Lupus Erythematosus

Keywords

Lupus Erythematosus,Systemic; Lupus Nephritis; Mesenchymal Stem Cells; Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Allogeneic MSC (AlloMSC)

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Natural Science Foundation of China

OTHER_GOV

Sponsor Role: collaborator

Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Nanjing University Medical College Affiliated Drum Tower Hospital

Principal Investigators

Lingyun Sun, M.D.

Role: STUDY_DIRECTOR

Nanjing University Medical College Affiliated Drum Tower Hospital

Locations

Department of Rheumatology and Immunology, Nanjing University Medical College Affiliated Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sun Lingyun, MD

Role: CONTACT

Phone: +86 25 83105219

Email: lingyunsun2001@yahoo.com.cn

Facility Contacts

Sun Lingyun, MD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 18389442 (View on PubMed)

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. doi: 10.1016/j.cellimm.2007.10.004. Epub 2007 Dec 3.

Reference Type: BACKGROUND

PMID: 18061155 (View on PubMed)

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. doi: 10.1177/0961203306075793.

Reference Type: BACKGROUND

PMID: 17402368 (View on PubMed)

Liang J, Zhang H, Kong W, Deng W, Wang D, Feng X, Zhao C, Hua B, Wang H, Sun L. Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study. Stem Cell Res Ther. 2018 Nov 14;9(1):312. doi: 10.1186/s13287-018-1053-4.

Reference Type: DERIVED

PMID: 30428931 (View on PubMed)

Other Identifiers

NSFC30772014

Identifier Type: -

Identifier Source: org_study_id