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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00010335

Collaborator

(none)

Enrollment

Location

Arm

125.9

Duration (Months)

Patients Per Site Per Month

Study Details

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.

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Sclerosis Systemic Lupus Erythematosus Dermatomyositis Juvenile Rheumatoid Arthritis Autoimmune Diseases	Procedure: Stem Cell Transplantation Device: CD34 selection	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2000

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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. Device: CD34 selection CD34+ cells are separated from the rest of the peripheral blood stem cells.

Arm

Intervention/Treatment

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.

Device: CD34 selection

CD34+ cells are separated from the rest of the peripheral blood stem cells.

Outcome Measures

Primary Outcome Measures

Mortality [Annually for 5 years and then every 5 years thereafter]

Secondary Outcome Measures

Immune reconstitution, engraftment, efficacy, late-effects [Annually for 5 years and then every 5 years thereafter]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 18 Years

Sexes Eligible for Study:

All

Accepts 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