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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

Primary Purpose

Systemic Sclerosis, Systemic Lupus Erythematosus, Dermatomyositis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Stem Cell Transplantation
CD34 selection
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Sclerosis focused on measuring arthritis & connective tissue diseases, dermatomyositis, immunologic disorders and infectious disorders, juvenile rheumatoid arthritis, rare disease, systemic lupus erythematosus, systemic sclerosis

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Participants will receive a stem cell transplant.

Outcomes

Primary Outcome Measures

Mortality

Secondary Outcome Measures

Immune reconstitution, engraftment, efficacy, late-effects

Full Information

First Posted
February 2, 2001
Last Updated
March 4, 2015
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00010335
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
November 2000 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Sclerosis, Systemic Lupus Erythematosus, Dermatomyositis, Juvenile Rheumatoid Arthritis, Autoimmune Diseases
Keywords
arthritis & connective tissue diseases, dermatomyositis, immunologic disorders and infectious disorders, juvenile rheumatoid arthritis, rare disease, systemic lupus erythematosus, systemic sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive a stem cell transplant.
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Transplantation
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
CD34 selection
Intervention Description
CD34+ cells are separated from the rest of the peripheral blood stem cells.
Primary Outcome Measure Information:
Title
Mortality
Time Frame
Annually for 5 years and then every 5 years thereafter
Secondary Outcome Measure Information:
Title
Immune reconstitution, engraftment, efficacy, late-effects
Time Frame
Annually for 5 years and then every 5 years thereafter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Woolfrey
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Carol A. Wallace, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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