Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases

Study Overview
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Brief Summary
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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.

Official Title
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Phase I/II Open-Label Monocentric Clinical Trial for Induction of Tolerance With CD34-Enriched Autologous Hematopoietic Stem Cell Transplantation After High-Dose Chemotherapy With Cyclophosphamide and Rabbit-Antithymocyte Globulin for Refractory Autoimmune Diseases

Conditions
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Autoimmune Diseases

Intervention / Treatment
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* Procedure: Autologous hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Treatment Group | Procedure: Autologous hematopoietic stem cell transplantation<br>* Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg)<br>* Other names: Stem cell selection: CliniMACS Device (Miltenyi Biotec, Bergisch Gladbach, Germany);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | 24 months | 
| Overall Survival |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Reconstitution |  | over 24 months | 
| Organ-specific response parameters |  | 24 months | 
| Serological Response (Autoantibodies) |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases