Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00282412
First received: January 24, 2006
Last updated: February 4, 2014
Last verified: February 2014

January 24, 2006
February 4, 2014
September 2002
September 2015   (final data collection date for primary outcome measure)
Tender joint count;Swollen joint count; Patient's global assessment of disease;Patient's assessment of pain;Patient's assessment of physical activity; (Health Assessment Questionnaire [HAQ]); Acute phase reactant value (erythrocyte sedimentation rate). [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]
  • 9. Patient’s assessment of physical activity (Health Assessment Questionnaire [HAQ])
  • 1. Tender joint count
  • 2. Swollen joint count
  • 3. Patient’s assessment of pain
  • 4. Patient’s global assessment of disease
  • 8. Physician global assessment
  • 7. Acute phase reactant value (erythrocyte sedimentation rate).
Complete list of historical versions of study NCT00282412 on ClinicalTrials.gov Archive Site
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Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism
Rheumatoid Arthritis: Tolerance Induction by Mixed Chimerism

Rheumatoid arthritis disease is believed to be due to immune cells, cells that normally protect the body and are now causing damage to the body. Risk of death is highest in people with twenty or more joints actively involved with disease, positive rheumatoid factor, an elevated sedimentation rate (laboratory measures of active inflammation), and patients with limitation of daily activities (trouble doing simple things like opening a carton of milk). In these high risk patients, life is significantly shortened. Death is usually from heart disease, kidney failure, neck dislocation, broken hip bones, or blood clots to the lung. In this study we use moderate dose chemotherapy (cyclophosphamide and fludarabine) and CAMPATH-1H (a protein that kills the immune cells that are thought to be causing the disease), followed by infusion of blood stem cells that have been collected from the patient's brother or sister (allogeneic stem cell transplant). The purpose of the moderate dose chemotherapy and CAMPATH-1H is to destroy the cells in the immune system and to allow the cells from the patient's brother or sister to grow. The purpose of the stem cell infusion is to restore blood cell production, which will be severely impaired by the moderate dose chemotherapy and CAMPATH-1H, and to produce a normal immune system that will no longer attack the body.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Rheumatoid Arthritis
Biological: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation
Experimental: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA
Intervention: Biological: Hematopoietic Stem Cell Transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
September 2016
September 2015   (final data collection date for primary outcome measure)

Participant Inclusion Criteria:

  1. Age > 18 and < 60 years at time of pre-transplant evaluation.
  2. An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria.
  3. Patients must have failed an autologous hematopoietic transplant or have failed to respond to either methotrexate or leflunomide in combination with a TNF inhibitor. Failure is defined as an inability to tolerate treatment with at least 6 swollen joints and 20 involved joints or inability to answer at least 70% of HAQ questions with "no difficulty" despite 2 or more months of treatment.
  4. Ability to give informed consent.
  5. Patient must have a HLA matched sibling donor at the A, B, C, and DR loci to proceed or HLA matched cord blood donor.
  6. If donor is HLA matched cord blood, cord blood stem cells will be obtained from the NMDP (1-800-548-1375) and one or two units of HLA matched cord blood will be infused on day zero.

Participant Exclusion Criteria

  1. History of coronary artery disease, or documented congestive heart failure.
  2. HIV positive.
  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 < 70% of predicted, DLCO < 40% of predicted.
  8. Resting LVEF < 45 %.
  9. Bilirubin > 2.0 mg/dl (unless due to Gilberts), transferase (AST) > 2.5 x upper limit of normal.
  10. Serum creatinine > 2.0 mg/dl.

Donor Exclusion Criteria

  1. Age < 18 years.
  2. Positive for HIV-1, HIV-2, HTLV-I, HTLV-II.
  3. Active hepatitis B or C.
  4. History of a malignancy except for a localized cancer such as skin cancer that is deemed cured.
  5. History of myocardial infarction or congestive heart failure.
  6. Inability to give informed consent.
  7. Current pregnancy.
Both
18 Years to 60 Years
No
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu
United States
 
NCT00282412
DIAD RA ALLO
Yes
Richard Burt, MD, Northwestern University
Northwestern University
Not Provided
Principal Investigator: Richard Burt, MD Northwestern University
Northwestern University
February 2014

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