Trial record 6 of 14 for:    RHEUMATOID ARTHRITIS, SYSTEMIC JUVENILE

Pilot Study of Total Body Irradiation in Combination With Cyclophosphamide, Anti-thymocyte Globulin, and Autologous CD34-Selected Peripheral Blood Stem Cell Transplantation in Children With Refractory Autoimmune Disorders

This study has been completed.
Sponsor:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00010335
First received: February 2, 2001
Last updated: May 25, 2011
Last verified: May 2011
  Purpose

OBJECTIVES: I. Determine the safety and long term complications of total body irradiation in combination with cyclophosphamide, anti-thymocyte globulin, and autologous CD34-selected peripheral blood stem cell (PBSC) transplantation in children with refractory autoimmune disorders.

II. Determine the efficacy of this treatment regimen in these patients. III. Determine the reconstitution of immunity after autologous CD34-selected PBSC transplantation in these patients.

IV. Determine engraftment of autologous CD34-selected PBSC in these patients.


Condition Intervention Phase
Systemic Sclerosis
Systemic Lupus Erythematosus
Dermatomyositis
Juvenile Rheumatoid Arthritis
Autoimmune Diseases
Procedure: 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: A Pilot Study of High-Dose Immunosuppression Followed by Infusion of CD34-Selected Autologous or Syngeneic Peripheral Blood Stem Cells for Treatment of Refractory Autoimmune Disorders

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Mortality [ Time Frame: Annually for 5 years and then every 5 years thereafter ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune reconstitution, engraftment, efficacy, late-effects [ Time Frame: Annually for 5 years and then every 5 years thereafter ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: November 2000
Study Completion Date: May 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive a stem cell transplant.
Procedure: Stem Cell Transplantation
Participants will receive a stem cell transplantation along with irradiation and the drugs anti-thymocyte globulin, cyclophosphamide, and filgrastim as noted in the text of this record.

Detailed Description:

PROTOCOL OUTLINE: This is a multicenter study. Patients receive filgrastim (G-CSF) subcutaneously daily until peripheral blood stem cell (PBSC) collection is completed. CD34+ cells are separated from the rest of the PBSCs.

Patients undergo total body irradiation twice daily on days -5 and -4. Patients receive anti-thymocyte globulin IV on days -5, -3, -1, 1, 3, and 5 and cyclophosphamide IV on days -3 and -2. CD34-selected PBSCs are reinfused on day 0. Patients receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

Patients are followed annually for 5 years and then every 5 years thereafter.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

  • Diagnosis of 1 of the following based on American College of Rheumatology (ACR) Criteria: Severe juvenile rheumatoid arthritis (systemic onset or polyarticular course) Juvenile systemic lupus erythematosus Systemic sclerosis Dermatomyositis
  • Refractory to standard or aggressive therapy OR unacceptable toxicity from standard therapy
  • Reasonable expectation of possible improvement as evidenced by a good potential for rehabilitation therapy and adequate social factors
  • No serious CNS damage that would preclude significant functional recovery

--Prior/Concurrent Therapy--

  • Chemotherapy: At least 4 weeks since prior methotrexate or cyclophosphamide
  • Endocrine therapy: At least 4 weeks since prior intra-arterial steroids Juvenile rheumatoid arthritis patients should continue steroids without taper throughout mobilization and harvest of stem cells If receiving corticosteroids, must be continued without taper

Other:

  • At least 4 weeks since prior anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) or sulfasalazine
  • At least 4 weeks since prior cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, penicillamine, or etanercept

--Patient Characteristics--

  • Life expectancy: At least 30 days
  • Hematopoietic: Absolute neutrophil count at least 1,000/mm3 OR Platelet count at least 100,000/mm3 No bone marrow aspirate or biopsy consistent with production defect (depletion of neutrophil precursors or megakaryocytes) No myelodysplasia
  • Hepatic: Bilirubin no greater than 2.5 mg/dL AST no greater than 300 U/L on two sequential tests No severe liver dysfunction within past month No active hepatitis A, B, or C
  • Renal: No end-stage glomerulonephritis or renal disease Creatinine clearance at least 40 mL/min
  • Cardiovascular: No uncontrolled malignant arrhythmia No New York Heart Association class III or IV congestive heart failure Ejection fraction at least 50%
  • Pulmonary: DLCO at least 45% (DLCO at least 70% for patients with pulmonary disease caused by documented processes other than primary autoimmune disorder, such as infectious pneumonia or aspiration pneumonia) No severe pulmonary hypertension (PAP greater than 50) without potential for significant improvement

Other:

  • No medical or psychosocial reasons that would make hematopoietic stem cell collection intolerable
  • No increased anesthetic risks
  • No fever higher than 39 degrees C
  • No positive serology for toxoplasmosis
  • No active life threatening infection not responsive to therapy
  • No other disease or organ dysfunction that would limit survival
  • No known hypersensitivity to murine or equine proteins
  • No known primary immunodeficiency disease HIV negative
  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: NCT00010335

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Ann Woolfrey Fred Hutchinson Cancer Research Center
Principal Investigator: Carol A. Wallace, MD Fred Hutchinson Cancer Research Center
  More Information

No publications provided

Responsible Party: Ann E. Woolfrey, MD / Associate Member, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00010335     History of Changes
Other Study ID Numbers: 1353.00, FHCRC-1353.00, 199/15575
Study First Received: February 2, 2001
Last Updated: May 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Fred Hutchinson Cancer Research Center:
arthritis & connective tissue diseases
dermatomyositis
immunologic disorders and infectious disorders
juvenile rheumatoid arthritis
rare disease
systemic lupus erythematosus
systemic sclerosis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Lupus Erythematosus, Systemic
Scleroderma, Systemic
Arthritis, Juvenile
Autoimmune Diseases
Dermatomyositis
Scleroderma, Diffuse
Sclerosis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Immune System Diseases
Myositis
Muscular Diseases
Polymyositis
Neuromuscular Diseases
Nervous System Diseases
Skin Diseases
Pathologic Processes
Antilymphocyte Serum
Cyclophosphamide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on August 21, 2014