Phase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)
Study Details
Study Description
Brief Summary
OBJECTIVES: I. Evaluate the safety and feasibility of treating mucopolysaccharidosis II (mild Hunter syndrome) by lymphocyte gene therapy.
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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).
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Determine the duration of survival of these transduced cells in these patients.
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics--
Mucopolysaccharidosis II (mild Hunter syndrome) as defined by the following:
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Characteristic coarse facial features, hepatosplenomegaly, and radiographic evidence of dysostosis multiplex
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Elevated urinary excretion of glycosaminoglycans in 3 urine specimens
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Deficient iduronate-2-sulfatase enzyme activity as measured in plasma and leukocytes
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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:
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Must have IQ score of 80 or higher
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Effective contraception required of all fertile patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Minnesota Medical School | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- University of Minnesota
Investigators
- Study Chair: Chester B. Whitley, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 199/13577
- UMN-HUNTER
- UMN-5P01HD32652