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

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ClinicalTrials.gov Identifier: NCT00750971
Recruitment Status : Recruiting
First Posted : September 11, 2008
Last Update Posted : March 20, 2017
Sponsor:
Information provided by (Responsible Party):
Falk Hiepe, Charite University, Berlin, Germany

Tracking Information
First Submitted Date  ICMJE September 10, 2008
First Posted Date  ICMJE September 11, 2008
Last Update Posted Date March 20, 2017
Study Start Date  ICMJE August 2008
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2008)
SLEDAI [ Time Frame: 48 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00750971 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2008)
  • Serologic response (autoantibodies) [ Time Frame: 48 months ]
  • Immune Reconstitution [ Time Frame: 48 months ]
  • Organ-specific response parameters [ Time Frame: 48 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE 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)
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 10, 2008)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00750971
Other Study ID Numbers  ICMJE CT-1306
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Falk Hiepe, Charite University, Berlin, Germany
Study Sponsor  ICMJE Charite University, Berlin, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Falk Hiepe, Prof Universitätsmedizin Charité
PRS Account Charite University, Berlin, Germany
Verification Date March 2017

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