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
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Hematopoietic Stem Cell Transplantation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rheumatoid Arthritis: Tolerance Induction by Mixed Chimerism

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 12
Study Start Date: September 2002
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA
Biological: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00282412

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

Locations
United States, Illinois
Northwestern University, Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00282412     History of Changes
Other Study ID Numbers: DIAD RA ALLO
Study First Received: January 24, 2006
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 01, 2014