Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Charite University, Berlin, Germany.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00750971
First received: September 10, 2008
Last updated: July 20, 2011
Last verified: August 2009

September 10, 2008
July 20, 2011
August 2008
August 2014   (final data collection date for primary outcome measure)
SLEDAI [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00750971 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)
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

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Systemic Lupus Erythematosus
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)
  • Experimental: 1
    Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
    Intervention: Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
  • Active Comparator: 2
    Best currently available immunosuppressive/immunomodulatory therapy
    Intervention: Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
August 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria
  2. Age between 18 and 60 years, inclusive
  3. Provision of informed consent
  4. 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:

  1. 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
  2. Ongoing cancer or history of malignancy within 5 years of screening
  3. Women who are pregnant or breastfeeding or use non-reliable methods of contraception
  4. Subjects with active systemic infection
  5. Subjects with history of active viral infection within 6 months prior to screening, known HIV-infection or chronic Hepatitis B or Hepatitis C
  6. History of allergic reaction to cyclophosphamide, G-CSF or ATG
  7. Use of immunosuppressive agents for indications other than SLE
  8. Any comorbidity that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy
Both
18 Years to 60 Years
No
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
Germany
 
NCT00750971
CT-1306
Yes
Charité Universitätsmedizin, Dept. of Rheumatology and Clinical Immunology
Charite University, Berlin, Germany
Not Provided
Principal Investigator: Falk Hiepe, Prof Universitätsmedizin Charité
Charite University, Berlin, Germany
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP