Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases (ASTRAD)
Primary Purpose
Autoimmune Diseases
Status
Unknown status
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Autologous hematopoietic stem cell transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Autoimmune Diseases focused on measuring ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases
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
Sites / Locations
- Charité Universitätsmedizin Berlin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A
Arm Description
Treatment Group
Outcomes
Primary Outcome Measures
Disease-free survival
Overall Survival
Secondary Outcome Measures
Immune Reconstitution
Organ-specific response parameters
Serological Response (Autoantibodies)
Full Information
NCT ID
NCT00742300
First Posted
August 26, 2008
Last Updated
November 21, 2008
Sponsor
Charite University, Berlin, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00742300
Brief Title
Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2008
Overall Recruitment Status
Unknown status
Study Start Date
January 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Charite University, Berlin, Germany
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Diseases
Keywords
ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
Treatment Group
Intervention Type
Procedure
Intervention Name(s)
Autologous hematopoietic stem cell transplantation
Other Intervention Name(s)
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)
Intervention Description
Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg)
Primary Outcome Measure Information:
Title
Disease-free survival
Time Frame
24 months
Title
Overall Survival
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Immune Reconstitution
Time Frame
over 24 months
Title
Organ-specific response parameters
Time Frame
24 months
Title
Serological Response (Autoantibodies)
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renate Arnold, Prof. Dr. med.
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Falk Hiepe, Prof. Dr. med.
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
11056673
Citation
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.
Results Reference
result
PubMed Identifier
15119545
Citation
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.
Results Reference
result
PubMed Identifier
11254005
Citation
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.
Results Reference
result
PubMed Identifier
18292651
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):22-7. doi: 10.1159/000117824. Epub 2008 Feb 22.
Results Reference
result
PubMed Identifier
11319598
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 cyclophosphamide-induced cardiomyopathy. Bone Marrow Transplant. 2001 Mar;27(6):657-8. doi: 10.1038/sj.bmt.1702829.
Results Reference
result
PubMed Identifier
18824594
Citation
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.
Results Reference
derived
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Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases
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