Induction of Tolerance with Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Severe Systemic Lupus Erythematosus (SLE) Refractory to Standard Immunosuppressive Therapy AN OPEN-LABEL, CONTROLLED, PHASE II MULTICENTER TRIAL OF IMMUNOABLATIVE CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE AND ANTI-THYMOCYTE GLOBULIN AND TRANSPLANTATION OF PURIFIED CD34+ AUTOLOGOUS HEMAPOIETIC STEM CELLS VERSUS CURRENTLY AVAILABLE IMMUNOSUPPRESSIVE THERAPY FOR THE TREATMENT OF REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS. - ASSIST

Conditions: Patients with systemic lupus erythematosus (SLE) will be under investigation who show high disease activity despite treatment with standard immunosuppressive therapies: high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months or mycophenolate mofetil (MMF) at doses of at least 2g/d for at least 6 months. Active disease is defined according to BILAG-scoring level A.

Registration Number: EUCTR2006-001269-40-DE

Lead Sponsor: Charité University Medicine

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 30

Inclusion Criteria

1. Diagnosis of SLE according to American College of Rheumatology (ACR)
classification criteria for SLE
2. Age between 18 and 60 years, inclusive
3. Provision of informed consent by subject or legally acceptable
representative
4. Severe disease, refractory to standard immunosuppressive therapy
defined as:
- failure of remission after treatment with high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months (defined as BILAG level A) for one of the following:
?Biopsy proven glomerulonephritis WHO class III or class IV
?Parenchymal disease of heart or lung
?Neuropsychiatric lupus
?Autoimmune cytopenia
OR
- recurrence of disease activity (defined as new BILAG level A) within one year of clinical remission in the presence of an adequate maintenance therapy (intravenous Cyclophosphamide, Mycophenolate Mofetil, Azathioprine, Methotrexate, IVIG, Cyclosporine, Rituximab)
in patients with persistent anti-dsDNA antibodies

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Severe concomitant disease or organ damage
a) Renal: chronic renal insufficiency with creatinine-clearance <40ml/min or serum
creatinine concentration >3mg/dl
b) Cardiac: congestive heart failure, LVEF < 40% determined by echocardiogram
uncontrolled arrhythmia
c) Pulmonary: mean PAP >50mmHg, TLCO/VA <40 % predicted
d) Gastrointestinal: liver cirrhosis (Child Pugh classification B or C)
2. Concurrent malignancy or history of malignancy within 5 years of
screening
3. Women who are pregnant or breastfeeding or use non-reliable
methods of contraception
4. Subjects with a history of viral infection (CMV, EBV, HCV) within 6
prior to screening, or known HIV-infection
5. History of allergy to cyclophosphamide or anti-thymocyte globulin