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

March 4, 2015 updated by: Fred Hutchinson Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mortality
Time Frame: Annually for 5 years and then every 5 years thereafter
Annually for 5 years and then every 5 years thereafter

Secondary Outcome Measures

Outcome Measure
Time Frame
Immune reconstitution, engraftment, efficacy, late-effects
Time Frame: Annually for 5 years and then every 5 years thereafter
Annually for 5 years and then every 5 years thereafter

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Investigators

  • Principal Investigator: Carol A. Wallace, MD, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2000

Primary Completion (ACTUAL)

July 1, 2010

Study Completion (ACTUAL)

May 1, 2011

Study Registration Dates

First Submitted

February 2, 2001

First Submitted That Met QC Criteria

February 1, 2001

First Posted (ESTIMATE)

February 2, 2001

Study Record Updates

Last Update Posted (ESTIMATE)

March 6, 2015

Last Update Submitted That Met QC Criteria

March 4, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1353.00
  • FHCRC-1353.00
  • 199/15575 (OTHER: ORD)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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