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 - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00010335

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 I

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Autoimmune Diseases Juvenile Rheumatoid Arthritis Lupus Rheumatoid Arthritis Scleroderma

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Further study details as provided by Office of Rare Diseases (ORD):

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
Estimated Study Completion Date:	December 2020
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00010335

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109
Contact: Ann Woolfrey 206-667-4453
Contact: Carol A. Wallace, MD 206-987-4448 cwallace@u.washington.edu

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:	Fred Hutchinson Cancer Research Center ( Ann E. Woolfrey, MD / Associate Member )
Study ID Numbers:	199/15575, FHCRC-1353.00
Study First Received:	February 2, 2001
Last Updated:	May 13, 2009
ClinicalTrials.gov Identifier:	NCT00010335 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Office of Rare Diseases (ORD):

arthritis & connective tissue diseases
dermatomyositis
immunologic disorders and infectious disorders
juvenile rheumatoid arthritis

rare disease
systemic lupus erythematosus
systemic sclerosis

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Arthritis, Rheumatoid
Cyclophosphamide
Myositis
Dermatomyositis
Pathologic Processes
Musculoskeletal Diseases
Lupus Erythematosus, Systemic
Neuromuscular Diseases
Therapeutic Uses
Arthritis
Connective Tissue Diseases

Polymyositis
Alkylating Agents
Arthritis, Juvenile Rheumatoid
Autoimmune Diseases
Immune System Diseases
Skin Diseases
Joint Diseases
Nervous System Diseases
Sclerosis
Rheumatic Diseases
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Muscular Diseases
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 27, 2009