Treatment of Refractory Systemic Lupus Erythematosus by Allogeneic Mesenchymal Stem Cells Derived From the Umbilical Cord (MSC-SLE)

This is an interventional treatment trial for Lupus Erythematosus Read More

Inclusion Criteria:

• Age > 18 years and < 70 years.
• Diagnosis of Systemic Lupus Erythematosus (SLE) according to the ACR criteria with positive antinuclear antibodies.
• Subjects with sustained disease activity defined by a SELENA- SLEDAI SLE activity index ≥ 6 at baseline,

• Inefficacy or adverse effects necessitating discontinuation of first and second line therapies of SLE including:

  a. Prednisone orally ≥ 6 mg / day (or equivalent) for at least 28 days. b. At least one or more of the following immunosuppressive therapies for 3 months in total: i- Cyclophosphamide, iv bolus ≥500 mg / month for 3 months minimum ii- Mycophenolate mofetil, orally or equivalent at a dose> 2000 mg / day for at least 90 days iii- Azathioprine orally at a dose> 2 mg / kg / day for at least 90 days; iv- Methotrexate orally or parenterally, at doses > 20mg / week for at least 90 days; v- Leflunomide orally, at a dose of> 10-mg / day for at least 90 days; vi- Rituximab (anti-CD20) intravenous bolus 375 mg / m2, once a week for four weeks or total dose of 1 g twice a day for two weeks vii- Cyclosporine orally, at a dose of 2.5-5 mg / kg / day, for at least 90 days; viii- Belimumab intravenously at monthly bolus of 10 mg / kg infusion), for at least 3 months.

• Patient who received treatment of SLE at stable doses for a minimum of 30 days prior to eligibility, including one of the following treatments: prednisone (or equivalent) alone or combined with antimalarial treatment, an anti-inflammatory steroidal and / or an immunosuppressant.
• Negative pregnancy test for women of childbearing age.
• For men and women : Using effective contraceptive methods during treatment and within 3 months after the end of treatment for men with her partner of childbearing age
• Signed Informed Consent.
• Affiliation to social security.

Exclusion Criteria:

1- Pregnancy, breastfeeding or lack of appropriate contraception during study duration

• Presence of:

  1. Renal failure: calculated creatinine clearance of <30 ml / min
  2. Cardiac failure: clinical signs of congestive heart failure; left ventricular ejection fraction <40% on echocardiography; uncontrolled ventricular arrhythmia;
  3. Hepatitis defined by abnormal levels of transaminases (AST, ALT> 2 x normal) not related to disease activity.
  4. Respiratory disease: mean PAP> 50 mmHg (echocardiography), respiratory failure defined by a resting blood pressure of oxygen at PaO 2 < 70 mmHg and / or PaCO2 > 50 mmHg without oxygen
• Severe psychiatric disorders, including severe psychosis related to SLE, which would prevent to give informed consent or to undergo the procedure.
• Active neoplasia or concomitant myelodysplasia, except for basal cell carcinoma or squamous cell carcinoma or in situ cervix carcinoma.
• Bone marrow failure defined by neutropenia <0.5.109/L, thrombocytopenia <30. 109 / L, anemia < 8 g / dL, lymphopenia CD4 + <200 x 106 / L caused by another disease than SLE.
• Acute or chronic uncontrolled infection: HIV 1/2, HTLV-1/2, Hepatitis B (HBsAg surface antigen), Hepatitis C with positive PCR
• Patient having received belimumab within 2 months of belimumab within 2 months of Baseline, or having received rituximab or other B cell depleting biologic therapy within 6 months of Baseline
• Current substance abuse or recent (within 60 days) history of substance abuse
• Patient in periods of exclusion from the national roster of researchers
• Patient with Linguistic or psychological incapacity to sign informed consent
• Patient already included in another study at the same time.
• Poor patient compliance.
• Patient under legal protection.