Phase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)

Mucopolysaccharidosis II Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004454
• Other study ID #: 199/13577
• Secondary ID: UMN-HUNTERUMN-5P
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 18, 1999
• Last updated: June 23, 2005
• Start date: October 1996

Study information

• Verified date: October 2003
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Genetic:
• lymphocyte gene therapy

Locations

Country	Name	City	State
United States	University of Minnesota Medical School	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	University of Minnesota - Clinical and Translational Science Institute

Country where clinical trial is conducted

United States,