Autoimmune Diseases
Conditions
Keywords
ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases
Brief summary
While glucocorticoids and immunosuppressants ameliorate manifestations of autoimmune diseases in many patients, current therapies are insufficient to control the disease in a subset of patients, and their clinical prognosis remains poor due to the development of vital organ failure, cumulative drug toxicity and to the increased risk of cardiovascular disease and malignancy. Immunoablative chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) has recently emerged as a promising experimental therapy for severely affected patients, providing them the potential to achieve treatment-free, long-term remission. The rationale for applying ASCT to autoimmune diseases has been the hope that immunoablation could eliminate inflammation-driving pathogenic cells from the immune system, and that regeneration of the patients' immune system from hematopoietic precursors could re-establish immunological tolerance.
Interventions
PROCEDUREAutologous hematopoietic stem cell transplantation
Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg)
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Autoimmune disease * Active disease with inadequate response to standard protocols (glucocorticoids and at least two different regimens of immunosuppressive drugs, such as intravenous cyclophosphamide 800-1000mg/application) * Provision of informed consent by subject
Exclusion criteria
* Active or chronic infections * Uncontrolled arrhythmia or congestive heart failure (ejection fraction below 50% determined by echocardiogram) * Lung fibrosis (transfer factor for carbon monoxide \[TLCO\] \<45%) * renal insufficiency (glomerular filtration rate below 40 ml/min) * Pulmonary arterial hypertension (\>40mmHg) * History of malignancy * Women who are pregnant or breastfeeding * Use non-reliable methods of contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival | 24 months |
| Overall Survival | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Immune Reconstitution | over 24 months |
| Organ-specific response parameters | 24 months |
| Serological Response (Autoantibodies) | 24 months |
Countries
Germany
Outcome results
None listed