Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST) - Full Text View

Purpose

While glucocorticoids and immunosuppressants ameliorate manifestations of SLE 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 investigators postulate that immunoablative therapy eliminates or effectively reduces the level of autoreactive T and B lymphocytes and then regeneration of de novo immunity resets the autoreactive immune system into a self-tolerant, protective immune system resulting in prolonged and treatment-free remission.

Condition	Intervention	Phase
Systemic Lupus Erythematosus	Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation	Phase II

MedlinePlus related topics:

Lupus

ChemIDplus related topics:

Cyclophosphamide Granulocyte colony-stimulating factor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title:	An Open-Label, Phase II Multicenter Cohort Study of Immunoablation With Cyclophosphamide and Antithymocyte-Globulin and Transplantation of Autologous Cd34-Enriched Hemapoietic Stem Cells Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Refractory Systemic Lupus Erythematosus

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

Primary Outcome Measures:

SLEDAI [ Time Frame: 48 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Serologic response (autoantibodies) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Immune Reconstitution [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Organ-specific response parameters [ Time Frame: 48 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	August 2008
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Immunoablation and Autologous Hematopoietic Stem Cell Transplantation	Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation Transplantation of purified CD34+ autologous hematopoietic stem cells mobilized with cyclophosphamide (200mg/m2)and G-CSF (10µg/kg/d) after immunoablation with cyclophosphamide (200mg/kg)and rabbit-antithymocyteglobulin (90mg/kg)
2: Active Comparator Best currently available immunosuppressive/immunomodulatory therapy	Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation Transplantation of purified CD34+ autologous hematopoietic stem cells mobilized with cyclophosphamide (200mg/m2)and G-CSF (10µg/kg/d) after immunoablation 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:

Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria
Age between 18 and 60 years, inclusive
Provision of informed consent
Active disease, refractory to standard immunosuppressive therapy defined as:
- BILAG level A and a SLEDAI-score of at least 10, despite treatment with high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months or mycophenolate mofetil (MMF) at doses of at least 2g -
- Lupus nephritis with renal biopsy performed within one year prior to screening showing glomerulonephritis WHO class III or IV
- Parenchymal disease of heart or lung
- Neuropsychiatric lupus
- Autoimmune cytopenia OR
- recurrence of disease activity (defined as BILAG level A and a SLEDAI of at least 10) within one year after successful induction therapy with cyclophosphamide or MMF in the presence of an adequate maintenance therapy with either cyclophosphamide (at least 500mg/m2 monthly), mycophenolate mofetil (at least 2g daily), azathioprine (at least 1.5mg/kg/d), methotrexate (at least 15mg weekly), cyclosporine (at least 3mg/kg/d) in patients with persistent anti-dsDNA antibodies

Exclusion Criteria:

Severe concomitant disease or organ damage
- renal: renal insufficiency with glomerular filtration rate below 40ml/min
- cardiac: congestive heart failure, LVEF < 40% determined by echocardiogram, uncontrolled arrhythmia
- pulmonary: mean pulmonary arterial pressure >50mmHg, DLCO < 40 % predicted
- gastrointestinal: liver cirrhosis; SGOT, SGPT greater than 2 x the upper limit of normal, unless due to active lupus
Ongoing cancer or history of malignancy within 5 years of screening
Women who are pregnant or breastfeeding or use non-reliable methods of contraception
Subjects with active systemic infection
Subjects with history of active viral infection within 6 months prior to screening, known HIV-infection or chronic Hepatitis B or Hepatitis C
History of allergic reaction to cyclophosphamide, G-CSF or ATG
Use of immunosuppressive agents for indications other than SLE
Any comorbidity that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00750971

Contacts


Contact: Falk Hiepe, Prof.	+49 30 450 513026	falk.hiepe@charite.de

Contact: Renate Arnold, Prof.	+49 30 450-553-302	renate.arnold@charite.de

Locations


Germany
	Universitätsklinikum Essen	Recruiting
	Essen, Germany, 45239 Essen
	Contact: Christoph Specker, Prof. +49 (0)201-84081214
	Principal Investigator: Christoph Specker, Prof.
	Universitätsklinik Düsseldorf	Recruiting
	Düsseldorf, Germany, 40225
	Contact: Mathias Schneider, Prof. +49 (0) 211-8117817
	Principal Investigator: Mathias Schneider, Prof.
	Universitätsklinik Heidelberg	Recruiting
	Heidelberg, Germany, 69120
	Contact: Hanns-Marting Lorenz, Prof. +49 (0) 6221-568044
	Principal Investigator: Hanns-Martin Lorenz, Prof.
	Universitätsklinik Köln	Recruiting
	Köln, Germany, 50937
	Contact: Andrea Rubbert-Roth, PD +49 (0) 221-4783993
	Principal Investigator: Andrea Rubbert-Roth, PD
	Universitätsmedizin Charité	Recruiting
	Berlin, Germany, 10117
	Contact: Falk Hiepe, Prof +49 30 450 513026
	Principal Investigator: Falk Hiepe, Prof.
	Universitätsklinik Tübingen	Recruiting
	Tübingen, Germany, 72026
	Contact: Ina Kötter, PD +49 (0) 7071-2984095
	Principal Investigator: Ina Kötter, PD
	Universitätsklinik Würzburg	Recruiting
	Würzburg, Germany, 97070
	Contact: Hans-Peter Tony, Prof. +49 (0) 931-20170420
	Principal Investigator: Hans-Peter Tony, Prof.
	Universitäsklinik Mainz	Recruiting
	Mainz, Germany, 55101
	Contact: Karin Kolbe, MD
	Principal Investigator: Karin Kolbe, MD

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators


Principal Investigator:	Falk Hiepe, Prof	Universitätsmedizin Charité

More Information

Publications:

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.

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.

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.

Responsible Party:	Dept. of Rheumatology and Clinical Immunology ( Charité Universitätsmedizin )
Study ID Numbers:	CT-1306
First Received:	September 10, 2008
Last Updated:	September 10, 2008
ClinicalTrials.gov Identifier:	NCT00750971
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Charite University, Berlin, Germany:

ASSIST

SLE

Stem Cell Transplantation

Tolerance

Study placed in the following topic categories:

Antilymphocyte Serum

Autoimmune Diseases

Lupus Erythematosus, Systemic

Connective Tissue Diseases

Cyclophosphamide

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action

Immunologic Factors

Immune System Diseases

Antineoplastic Agents

Therapeutic Uses

Physiological Effects of Drugs

Myeloablative Agonists

Antineoplastic Agents, Alkylating

Antirheumatic Agents

Alkylating Agents

Immunosuppressive Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 06, 2008

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00750971