OBJECTIVES: I. Determine the toxicity of high-dose cyclophosphamide, anti-thymocyte globulin, and total body irradiation with T-cell-depleted autologous bone marrow rescue in patients with high-risk rheumatoid arthritis. II. Determine the safety and efficacy of this regimen in this patient population.

Condition	Treatment or Intervention	Phase
Rheumatoid Arthritis Juvenile Rheumatoid Arthritis	Drug: anti-thymocyte globulin  Drug: cyclophosphamide  Drug: filgrastim  Procedure: Autologous Bone Marrow Transplantation	Phase I

Further Study Details: 

Expected Total Enrollment:  10

PROTOCOL OUTLINE: Patients undergo peripheral blood stem cell (PBSC) harvest after induction therapy. Patients receive 2 doses of cyclophosphamide IV over 1 hour given 3 hours apart followed 24 hours later by filgrastim (G-CSF) subcutaneously (SC). G-CSF continues daily until after leukapheresis. Harvested PBSCs then undergo T-lymphocyte depletion. Patients undergo conditioning regimen of total body irradiation on day -6, cyclophosphamide IV over 1 hour on days -5 through -2 and anti-thymocyte globulin IV over 12 hours beginning 10 hours after cyclophosphamide on days -4 through -2. Lymphocyte-depleted PBSCs are reinfused on day 0. Patients also receive G-CSF SC daily beginning on day 0 and continuing until blood counts recover. Patients are followed at 1, 2, 3, 6, and 12 months and then annually for 5 years.

Ages Eligible for Study:  up to  59 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria Positive rheumatoid factor
• Treatment failure following therapy with 2 of the following disease-modifying agents: Methotrexate Azathioprine Plaquenil Asulfidine Gold D-penicillamine
• Must have 6 swollen joints from active rheumatoid arthritis AND EITHER 30 or more involved joints (swelling, tenderness, deformity, pain on motion, or decreased motion) OR Responded "without any difficulty" to less than 75% of questions on Health Assessment Questionnaire
• Juvenile rheumatoid arthritis allowed if onset of disease is either polyarthritic or systemic Must have at least 6 swollen joints Treatment failure after corticosteroids and 2 disease-modifying agents

--Patient Characteristics--

• Age: Under 60 at time of pretransplantation evaluation
• Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 2.0 mg/dL AST no greater than 2 times upper limit of normal
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No coronary artery disease or congestive heart failure Resting LVEF at least 45%
• Pulmonary: FEV1/FVC at least 75% predicted DLCO at least 50% predicted
• Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception Must be willing to accept and/or comprehend irreversible sterility as a side effect of therapy HIV negative No uncontrolled diabetes mellitus No other concurrent medical illness that would preclude study No concurrent psychiatric illness or mental deficiency that would preclude study No history of malignancy except localized basal cell or squamous cell skin cancer (malignancies such as head and neck cancer and stage I breast cancer curatively treated with local surgical excision considered on an individual basis) No known history of allergy to eggs or murine proteins No known hypersensitivity to E.coli-derived proteins

Illinois
      Northwestern Memorial Hospital, Chicago,  Illinois,  60611,  United States; Recruiting
      Northwestern University Medical School, Chicago,  Illinois,  60611,  United States; Recruiting
Wisconsin
      University of Wisconsin Hospital and Clinics, Madison,  Wisconsin,  53792-0001,  United States; Recruiting

Study chairs or principal investigators

Richard K. Burt,  Study Chair,  Northwestern Memorial Hospital   

Study ID Numbers:  199/14973; NU-96RA1
Record last reviewed:  January 2005
Last Updated:  January 21, 2005
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017615
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08