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Stem Cell Support in Patients With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00278551
Recruitment Status : Terminated
First Posted : January 18, 2006
Last Update Posted : April 8, 2013
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University

Tracking Information
First Submitted Date  ICMJE January 15, 2006
First Posted Date  ICMJE January 18, 2006
Last Update Posted Date April 8, 2013
Study Start Date  ICMJE June 1997
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2008)
Tender joint count; Swollen joint count; Patient's assessment of pain;Patient's global assessment of disease; Physician global assessment;Acute phase reactant value (erythrocyte sedimentation rate). [ Time Frame: 5 years after transplant ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2006)
  • 1. Tender joint count
  • 2. Swollen joint count
  • 3. Patient's assessment of pain
  • 4. Patient's global assessment of disease
  • 5. Physician global assessment
  • 6. Patient's assessment of physical activity (Health Assessment Questionnaire [HAQ])
  • 7. Acute phase reactant value (erythrocyte sedimentation rate).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Stem Cell Support in Patients With Rheumatoid Arthritis
Official Title  ICMJE Immune Ablation and Hematopoietic Stem Cell Support in Patients With Rheumatoid Arthritis and High Risk Factors
Brief Summary Rheumatoid arthritis (RA) is a chronic illness, immunologically mediated, probably induced by the exposure to an antigen or antigens, to which immunologic tolerance is lost. The disease has a variable course, from a mild, intermittently symptomatic illness requiring only symptomatic therapy to a fulminant illness requiring dangerous immunosuppressive therapy, surgery or both. The molecular defect causing RA has not been characterized, but may involve aberrant T cell, B cell, and macrophage function. Although RA often responds to immunosuppressive medication including corticosteroids, methotrexate, azathioprine and cyclophosphamide, or to non-steroidal anti-inflammatory drugs, no therapy has been curative. In patients with severe RA, who have been unresponsive to corticosteroids, and who have more than 20 active joints or vasculitis, we propose, as a phase I-II study, complete immune ablation and subsequent reconstitution with autologous in vitro T lymphocyte depleted PBSCs harvested from the patient prior to immune ablation. The combination of high dose cyclophosphamide and anti-thymocyte globulin conditioning will be followed by rescue with autologous lymphocyte depleted PBSCs. Subsequent disease activity will be followed by: (1) RA disease activity index, (2) type and amount of therapy for RA, and (3) flow cytometry of peripheral blood lymphocyte subsets, (4) joint count, (5) patients' assessment of pain, (6) arthritis impact measurement scales (AIMS) questionnaire, (7) acute phase reactants. This study will dose standard therapy, i.e. immune suppression, to the point of complete immune ablation and subsequent recapitulation of lymphocyte ontogeny by PBSC rescue. We anticipate that this study will also form the basis to clarify further the role of the immune system in RA.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Intervention  ICMJE Biological: Immune ablation and hematopoietic stem cell transplant
Autologous Hematopoietic Stem Cell Transplant
Study Arms  ICMJE Experimental: heatopoietic stem cell transplant
Intervention: Biological: Immune ablation and hematopoietic stem cell transplant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 15, 2006)
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Physiologic age < 60 years old or >18 years old.
  2. An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria, and a positive rheumatoid factor will be required.
  3. Patients must have failed two disease-modifying agents, such as methotrexate, plaquenil, gold, azathioprine, asulfidine or D-penicillamine.
  4. Patients must have six (6) swollen joints from active RA and either thirty (30) or greater involved joints (swelling, tenderness, deformity, pain on motion, or decreased motion), or have answered less than 75 percent of Health Assessment Questionnaire (HAQ) questions "without any difficulty."
  5. A harvest of PBSC greater than 1.4 x 106 CD34+ cells /kg after CD34+ selection will be necessary for the patient to proceed to transplant.
  6. Ability to give informed consent
  7. Patients with Juvenile Rheumatoid Arthritis (JRA) will be candidates if disease onset is polyarthritic or systemic and they have at least 6 swollen joints and have failed corticosteroids and two disease-modifying drugs

Exclusion Criteria:

  1. HIV positive
  2. History of coronary artery disease, or congestive heart failure.
  3. Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemoradiotherapy
  4. Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis.
  5. Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
  6. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  7. FEV1/FVC < 75% of predicted, DLCO < 50% of predicted.
  8. Resting LVEF < 45 %
  9. Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal
  10. Serum creatinine > 2.0 mg/dl
  11. Platelet count less than 100,000/ul, ANC less than 1000/ul
  12. History of allergy to eggs or murine proteins
  13. Known hypersensitivity to E. coli derived proteins
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00278551
Other Study ID Numbers  ICMJE NU 96RA1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Burt, MD, Northwestern University
Study Sponsor  ICMJE Richard Burt, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard Burt, MD Northwestern University
PRS Account Northwestern University
Verification Date April 2013

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