Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases

NCT00742300 | Unknown Phase 1

• 1 other identifier: CT-0198
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Diseases

Keywords

ASCT; Tolerance induction; SLE; Transplantation; Autoimmune diseases

Outcome Measures

Primary Outcomes (2)

• Disease-free survival

  24 months

• Overall Survival

  24 months

Secondary Outcomes (3)

• Immune Reconstitution

  over 24 months

• Organ-specific response parameters

  24 months

• Serological Response (Autoantibodies)

  24 months

Study Arms (1)

A

EXPERIMENTAL

Treatment Group

Procedure: Autologous hematopoietic stem cell transplantation

Interventions

Autologous hematopoietic stem cell transplantation PROCEDURE

Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg)

Also known as: 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)

A

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Publications (6)

• 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.

  PMID: 11056673 RESULT

• 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.

  PMID: 15119545 RESULT

• 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.

  PMID: 11254005 RESULT

• 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.

  PMID: 18292651 RESULT

• 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.

  PMID: 11319598 RESULT

• 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.

  PMID: 18824594 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Renate Arnold, Prof. Dr. med.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Falk Hiepe, Prof. Dr. med.

  Charite University, Berlin, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 27, 2008
• Study Start: January 1, 1998
• Last Updated: November 24, 2008

Record last verified: 2008-11

Locations

DE (1)