Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases - Full Text View

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00742300

Purpose

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	Intervention	Phase
Autoimmune Diseases	Procedure: Autologous hematopoietic stem cell transplantation	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Autoimmune Diseases

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Disease-free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Overall Survival [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immune Reconstitution [ Time Frame: over 24 months ] [ Designated as safety issue: No ]
Organ-specific response parameters [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Serological Response (Autoantibodies) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Study Start Date:

January 1998

Arms	Assigned Interventions
A: Experimental 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)

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00742300

Locations

Germany
Charité Universitätsmedizin Berlin
Berlin, Germany, 10117

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator:	Renate Arnold, Prof. Dr. med.	Charité Universitätsmedizin Berlin
Study Chair:	Falk Hiepe, Prof. Dr. med.	Charité Universitätsmedizin Berlin

More Information

Publications:

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. Arthritis Res. 2000;2(4):327-36. 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.

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

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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. Epub 2008 Sep 29.

Responsible Party:	Charité Universitätsmedizin Berlin ( Christoph Krukenkamp )
Study ID Numbers:	CT-0198
Study First Received:	August 26, 2008
Last Updated:	November 21, 2008
ClinicalTrials.gov Identifier:	NCT00742300 History of Changes
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Charite University, Berlin, Germany:

ASCT
Tolerance induction
SLE
Transplantation
Autoimmune diseases

Study placed in the following topic categories:

Antilymphocyte Serum
Autoimmune Diseases
Immunologic Factors
Antineoplastic Agents, Alkylating

Cyclophosphamide
Antirheumatic Agents
Alkylating Agents
Immunosuppressive Agents

Additional relevant MeSH terms:

Autoimmune Diseases
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide

Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on July 06, 2009