ASTRAD: Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Unknown status

CT.gov ID

NCT00742300

Collaborator

(none)

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases	Procedure: Autologous hematopoietic stem cell transplantation	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 1998

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Treatment Group	Procedure: Autologous 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) Other Names: Mobilization: 2.0 g/m2 Cyclophosphamide followed by daily G-CSF (10 µg/kg, Amgen, Thousand Oaks, CA) Conditioning: 200mg/kg Cyclophosphamide (Endoxan), 90mg/kg rabbit-antithymocyteglobulin (ATG, Fresenius, Bad Homburg, Germany) Stem cell selection: CliniMACS Device (Miltenyi Biotec, Bergisch Gladbach, Germany)

Arm

Intervention/Treatment

Experimental: A

Treatment Group

Procedure: Autologous 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)

Other Names:

Mobilization: 2.0 g/m2 Cyclophosphamide followed by daily G-CSF (10 µg/kg, Amgen, Thousand Oaks, CA)

Conditioning: 200mg/kg Cyclophosphamide (Endoxan), 90mg/kg rabbit-antithymocyteglobulin (ATG, Fresenius, Bad Homburg, Germany)

Stem cell selection: CliniMACS Device (Miltenyi Biotec, Bergisch Gladbach, Germany)

Outcome Measures

Primary Outcome Measures

Disease-free survival [24 months]
Overall Survival [24 months]

Secondary Outcome Measures

Immune Reconstitution [over 24 months]
Organ-specific response parameters [24 months]
Serological Response (Autoantibodies) [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charité Universitätsmedizin Berlin	Berlin		Germany	10117

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator: Renate Arnold, Prof. Dr. med., Charite University, Berlin, Germany
Study Chair: Falk Hiepe, Prof. Dr. med., Charite University, Berlin, Germany