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.
Conditions
Interventions
Pharmaceutical Form:
Sponsors
Charité University Medicine
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria: 1. Severe concomitant disease or organ damage a) Renal: chronic renal insufficiency with creatinine-clearance 3mg/dl b) Cardiac: congestive heart failure, LVEF 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and efficacy of immunoablation with antithymocyte globulin and cyclophosphamied followed by autologous hematopoietic stem cell transplantation versus treatment with currently available immunosuppressive/immunomodulatory therapy for refractory SLE ;Secondary Objective: - To assess durability of clinical response with respect to percentage and number of subjects showing complete remission at Month 48, defined as SLEDAI less than 3 in the absence of immunosuppressive therapy and prednisolone dosage = 7.5mg daily. - To assess time-point and number of patients with relapse, defined as increase in prednisolone dosage >10mg/d (for SLE treatment) or increase in SLEDAI by at least 3 compared to previous visit - To assess serological response including serum autoantibody titers and complement levels C3, C4 - To assess health related Quality of Life - To assess organ specific response parameters based on individual SLE manifestations - To assess immune reconstitution - To search for predictive factors favouring long-term remission ;Primary end point(s): SLE patients achieving complete clinical remission at Month 24 after autologous hematopoietic stem cell transplantation, defined as SLEDAI less than 3 in the absence of immunosuppressive therapy and prednisolone = 5mg daily. | — |
Countries
Germany
Outcome results
None listed