Phase I/II Study of Retroviral-Mediated Transfer of Iduro... | NCT00004454

Status Module

Record Verification Date

Oct 2003

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Oct 1996

Primary Completion Date

Not provided

Completion Date

Not provided

First Submitted Date

Oct 18, 1999

First Submission Date that Met QC Criteria

Oct 18, 1999

First Posted Date

Oct 19, 1999Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jun 23, 2005

Last Update Posted Date

Jun 24, 2005Estimated

Name	Class
University of Minnesota	OTHER

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1Phase 2

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

No data available

No data is available for this block.

Enrollment

Name	Type	Description	Arm Group Labels	Other Names
lymphocyte gene therapy	Genetic

Eligibility Module

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Name	Affiliation	Role
Chester B. Whitley	University of Minnesota	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota Medical School		Minneapolis	Minnesota	55455	United States

ID	Term
D016532	Mucopolysaccharidosis II
D008661	Metabolism, Inborn Errors
D009083	Mucopolysaccharidoses
D035583	Rare Diseases

Ancestor Terms

ID	Term
D038901	X-Linked Intellectual Disability
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D020271	Heredodegenerative Disorders, Nervous System
D002239	Carbohydrate Metabolism, Inborn Errors
D016464	Lysosomal Storage Diseases
D017520	Mucinoses
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Type	Description	Link
UMN-HUNTER
UMN-5P01HD32652