Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases (ASTRAD)

• ClinicalTrials.gov Identifier: NCT00742300
• Recruitment Status: Unknown
• First Posted: August 27, 2008
• Last Update Posted: November 24, 2008
• Sponsor: Charite University, Berlin, Germany
• Information provided by: Charite University, Berlin, Germany

Tracking Information

• First Submitted Date: August 26, 2008
• First Posted Date: August 27, 2008
• Last Update Posted Date: November 24, 2008
• Study Start Date: January 1998
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: August 26, 2008)

• Disease-free survival [ Time Frame: 24 months ]
• Overall Survival [ Time Frame: 24 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 26, 2008)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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)

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)

Study Arms

Experimental: A

Treatment Group

Intervention: Procedure: Autologous hematopoietic stem cell transplantation

Publications *

• Rosen O, Thiel A, Massenkeil G, Hiepe F, Haupl 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. Arthritis Res. 2000;2(4):327-36. doi: 10.1186/ar107. Epub 2000 Jun 8.
• 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, Saccardi R, Schneider P, Zintl F, Gratwohl A, Tyndall A; European Group for Blood and Marrow Transplantation; European League Against Rheumatism Registry. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus. 2004;13(3):168-76. doi: 10.1191/0961203304lu525oa.
• Rosen O, Hiepe F, Massenkeil G, Thiel A, Arnold R. Relapse of systemic lupus erythematosus. Lancet. 2001 Mar 10;357(9258):807-8. doi: 10.1016/S0140-6736(05)71239-3. No abstract available.
• 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):22-7. doi: 10.1159/000117824. Epub 2008 Feb 22.
• 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 cyclophosphamide-induced cardiomyopathy. Bone Marrow Transplant. 2001 Mar;27(6):657-8. doi: 10.1038/sj.bmt.1702829.
• Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, Mei H, Radtke H, Gromnica-Ihle E, Burmester GR, Arnold R, Radbruch A, Hiepe F. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009 Jan 1;113(1):214-23. doi: 10.1182/blood-2008-07-168286. Epub 2008 Sep 29.

Recruitment Information

• Recruitment Status: Unknown status
• Enrollment: Not Provided
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT00742300
• Other Study ID Numbers: CT-0198
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Christoph Krukenkamp, Charité Universitätsmedizin Berlin
• Original Responsible Party: Same as current
• Current Study Sponsor: Charite University, Berlin, Germany
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Charite University, Berlin, Germany
• Verification Date: November 2008