Clinical trial NCT00698191: Mesenchymal Stem Cells Transplantation for Refractory Systemic Lupus Erythematosus (SLE)
Official title: Phase I/IIa: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells Transplantation For Refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Refractory Systemic Lupus Erythematosus
Keywords: Lupus Erythematosus,Systemic
Lupus Nephritis
Mesenchymal Stem Cells
Transplantation
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2008-06-17
Enrollment: 20
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
timeFrame: Monthly
measure: Lupus serology (ANA, dsDNA, C3, C4)
timeFrame: Monthly
measure: Renal function (GFR, BUN, urinalysis)
timeFrame: Monthly
Secondary outcomes:
measure: Percentage of systemic T regulatory population
timeFrame: Every 3 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Department of Rheumatology and Immunology, Nanjing University Medical College Affiliated Drum Tower Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing University Medical College Affiliated Drum Tower Hospital
name: Lingyun Sun, M.D.
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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. doi: 10.1177/0961203306075793.
citation: 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.