Stem Cell Support in Patients With Rheumatoid Arthritis - Full Text View

Sponsor:	Richard Burt
Information provided by (Responsible Party):	Richard Burt, Northwestern University
ClinicalTrials.gov Identifier:	NCT00278551

Purpose

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.

Condition	Intervention	Phase
RHEUMATOID ARTHRITIS	Procedure: Immune ablation and hematopoietic stem cell transplant	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Immune Ablation and Hematopoietic Stem Cell Support in Patients With Rheumatoid Arthritis and High Risk Factors

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	June 1997
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Autologous Hematopoietic Stem Cell Transplant

Eligibility

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

Criteria

Inclusion Criteria:

Physiologic age < 60 years old or >18 years old.
An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria, and a positive rheumatoid factor will be required.
Patients must have failed two disease-modifying agents, such as methotrexate, plaquenil, gold, azathioprine, asulfidine or D-penicillamine.
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."
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.
Ability to give informed consent
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:

HIV positive
History of coronary artery disease, or congestive heart failure.
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
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.
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.
Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
FEV1/FVC < 75% of predicted, DLCO < 50% of predicted.
Resting LVEF < 45 %
Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal
Serum creatinine > 2.0 mg/dl
Platelet count less than 100,000/ul, ANC less than 1000/ul
History of allergy to eggs or murine proteins
Known hypersensitivity to E. coli derived proteins

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278551

Contacts

Contact: Dzemila Spahovic, MD

312-908-0059

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

Richard Burt

Investigators

Principal Investigator:

Richard Burt, MD

Northwestern University

More Information

No publications provided

Responsible Party:	Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:	NCT00278551 History of Changes
Obsolete Identifiers:	NCT00017615
Other Study ID Numbers:	NU 96RA1
Study First Received:	January 15, 2006
Last Updated:	August 29, 2011
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 February 12, 2012