Back to resultsPhase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)
Primary Purpose
Mucopolysaccharidosis II
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lymphocyte gene therapy
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis II focused on measuring inborn errors of metabolism, mucopolysaccharidosis, mucopolysaccharidosis II, rare disease
Eligibility Criteria
PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Mucopolysaccharidosis II (mild Hunter syndrome) as defined by the following: Characteristic coarse facial features, hepatosplenomegaly, and radiographic evidence of dysostosis multiplex Elevated urinary excretion of glycosaminoglycans in 3 urine specimens Deficient iduronate-2-sulfatase enzyme activity as measured in plasma and leukocytes Mutation consistent with mild Hunter syndrome must have either: A single base substitution of the coding sequence not previously associated with severe Hunter syndrome phenotype OR An exon-skipping mutation that would allow for occasional production of (minimal amounts of) normal protein --Patient Characteristics-- Cardiovascular: No severe cardiac disease Pulmonary: No severe respiratory disease Other: Must have IQ score of 80 or higher Effective contraception required of all fertile patients
Sites / Locations
- University of Minnesota Medical School
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00004454
First Posted
October 18, 1999
Last Updated
June 23, 2005
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT00004454
Brief Title
Phase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2003
Overall Recruitment Status
Completed
Study Start Date
October 1996 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
University of Minnesota
4. Oversight
5. Study Description
Brief Summary
OBJECTIVES: I. Evaluate the safety and feasibility of treating mucopolysaccharidosis II (mild Hunter syndrome) by lymphocyte gene therapy.
II. Determine the levels of iduronate-2-sulfatase enzyme in these patients attained by infusing increasing doses of lymphocytes transduced with a retroviral vector designed for insertion and expression of this iduronate-2-sulfatase gene (L2SN).
III. Determine the duration of survival of these transduced cells in these patients.
IV. Determine whether monthly infusion of L2SN-transduced lymphocytes accomplishes metabolic correction (as measured by glycosaminoglycan excretion), decrease in liver or spleen volume, any therapeutic effect upon cardiac and pulmonary dysfunction, or any other effects from treatment.
Detailed Description
PROTOCOL OUTLINE: Peripheral blood lymphocytes are harvested from patient by apheresis, stimulated to initiate the growth of T-lymphocytes, transduced with retrovirus L2SN containing iduronate-2-sulfatase, and reinfused into the patient.
Patients receive 12 monthly infusions of these retroviral-mediated gene transduced lymphocytes with the first three infusions in a dose escalation format.
Patients are monitored for at least 2 hours after completion of each infusion. Patients are followed at 1 year after treatment, and then until death.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis II
Keywords
inborn errors of metabolism, mucopolysaccharidosis, mucopolysaccharidosis II, rare disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Enrollment
2 (false)
8. Arms, Groups, and Interventions
Intervention Type
Genetic
Intervention Name(s)
lymphocyte gene therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics--
Mucopolysaccharidosis II (mild Hunter syndrome) as defined by the following:
Characteristic coarse facial features, hepatosplenomegaly, and radiographic evidence of dysostosis multiplex
Elevated urinary excretion of glycosaminoglycans in 3 urine specimens
Deficient iduronate-2-sulfatase enzyme activity as measured in plasma and leukocytes
Mutation consistent with mild Hunter syndrome must have either: A single base substitution of the coding sequence not previously associated with severe Hunter syndrome phenotype OR An exon-skipping mutation that would allow for occasional production of (minimal amounts of) normal protein
--Patient Characteristics--
Cardiovascular: No severe cardiac disease
Pulmonary: No severe respiratory disease
Other:
Must have IQ score of 80 or higher
Effective contraception required of all fertile patients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chester B. Whitley
Organizational Affiliation
University of Minnesota
Official's Role
Study Chair
Facility Information:
Facility Name
University of Minnesota Medical School
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)
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