Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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
Experimental: 1
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)
Active Comparator: 2
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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Universitätsmedizin Charité Recruiting
Berlin, Germany, 10117
Contact: Falk Hiepe, Prof    +49 30 450 513026      
Principal Investigator: Falk Hiepe, Prof.         
Universitätsklinik Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Contact: Mathias Schneider, Prof.    +49 (0) 211-8117817      
Principal Investigator: Mathias Schneider, Prof.         
Universitätsklinikum Essen Recruiting
Essen, Germany, 45239 Essen
Contact: Christoph Specker, Prof.    +49 (0)201-84081214      
Principal Investigator: Christoph Specker, 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         
Universitäsklinik Mainz Recruiting
Mainz, Germany, 55101
Contact: Karin Kolbe, MD         
Principal Investigator: Karin Kolbe, MD         
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.         
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Falk Hiepe, Prof Universitätsmedizin Charité
  More Information

Publications:

Responsible Party: Charité Universitätsmedizin, Dept. of Rheumatology and Clinical Immunology
ClinicalTrials.gov Identifier: NCT00750971     History of Changes
Other Study ID Numbers: CT-1306
Study First Received: September 10, 2008
Last Updated: July 20, 2011
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Charite University, Berlin, Germany:
ASSIST
SLE
Stem Cell Transplantation
Tolerance

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Cyclophosphamide
Immunosuppressive Agents
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014