Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases

Autoimmune Diseases Clinical Trial

— ASTRAD  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00742300
• Other study ID #: CT-0198
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: August 26, 2008
• Last updated: November 21, 2008
• Start date: January 1998

Study information

• Verified date: November 2008
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoimmune Diseases

Intervention

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)

Locations

Country	Name	City	State
Germany	Charité Universitätsmedizin Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (5)

Jayne D, Passweg J, Marmont A, Farge D, Zhao X, Arnold R, Hiepe F, Lisukov I, Musso M, Ou-Yang J, Marsh J, Wulffraat N, Besalduch J, Bingham SJ, Emery P, Brune M, Fassas A, Faulkner L, Ferster A, Fiehn C, Fouillard L, Geromin A, Greinix H, Rabusin M, Sacc — View Citation

Rosen O, Hiepe F, Massenkeil G, Thiel A, Arnold R. Relapse of systemic lupus erythematosus. Lancet. 2001 Mar 10;357(9258):807-8. — View Citation

Rosen O, Massenkeil G, Hiepe F, Pest S, Hauptmann S, Radtke H, Burmester G, Thiel A, Radbruch A, Heymer B, Arnold R. Cardiac death after autologous stem cell transplantation (ASCT) for treatment of systemic sclerosis (SSc): no evidence for cyclophosphamid — View Citation

Rosen O, Thiel A, Massenkeil G, Hiepe F, Häupl T, Radtke H, Burmester GR, Gromnica-Ihle E, Radbruch A, Arnold R. Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells — View Citation

Thiel A, Alexander T, Schmidt CA, Przybylski GK, Kimmig S, Kohler S, Radtke H, Gromnica-Ihle E, Massenkeil G, Radbruch A, Arnold R, Hiepe F. Direct assessment of thymic reactivation after autologous stem cell transplantation. Acta Haematol. 2008;119(1):22 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival		24 months	No
Primary	Overall Survival		24 months	Yes
Secondary	Immune Reconstitution		over 24 months	No
Secondary	Organ-specific response parameters		24 months	No
Secondary	Serological Response (Autoantibodies)		24 months	No