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

This study has been completed.

First Received: October 18, 1999 Last Updated: June 23, 2005 History of Changes

Sponsors and Collaborators:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) University of Minnesota
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004454

Purpose

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.

Condition	Intervention	Phase
Mucopolysaccharidosis II	Gene Transfer: lymphocyte gene therapy	Phase I Phase II

Genetics Home Reference related topics: L1 syndrome mucopolysaccharidosis type II

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	2
Study Start Date:	October 1996

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004454

Locations

United States, Minnesota
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

More Information

No publications provided

Study ID Numbers:	199/13577, UMN-HUNTER, UMN-5P01HD32652
Study First Received:	October 18, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00004454 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

inborn errors of metabolism
mucopolysaccharidosis
mucopolysaccharidosis II
rare disease

Study placed in the following topic categories:

Mucopolysaccharidosis II
Metabolic Diseases
Lysosomal Storage Diseases
Rare Diseases
Mucopolysaccharidosis Type II
Mental Retardation
Metabolism, Inborn Errors
Mucopolysaccharidoses

Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Connective Tissue Diseases
Genetic Diseases, X-Linked
Neurologic Manifestations
Metabolic Disorder
Neurobehavioral Manifestations
Hunter-McAlpine Syndrome

Additional relevant MeSH terms:

Mucopolysaccharidosis II
Metabolic Diseases
Lysosomal Storage Diseases
Nervous System Diseases
Mucinoses
Mental Retardation
Metabolism, Inborn Errors
Mucopolysaccharidoses

Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Connective Tissue Diseases
Neurologic Manifestations
Mental Retardation, X-Linked
Carbohydrate Metabolism, Inborn Errors
Neurobehavioral Manifestations

ClinicalTrials.gov processed this record on May 07, 2009