Stem Cell Transplant w/Laronidase for Hurler

Phase II Study of Combined Laronidase (AldurazymeTM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH)

The investigators hypothesize that weekly infusions of Laronidase ERT for 10-12 weeks prior to transplant and 8 weeks following transplant will result in a reduction of glycosaminoglycans (GAG) burden that is associated with decreased complications following transplant.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I; Hurler Syndrome
• Intervention / Treatment: Procedure: Stem Cell Transplant; Drug: Laronidase ERT

Detailed Description

Subjects will receive laronidase once a week intravenously for 10-12 weeks prior to transplant and for approximately 8 weeks after transplant. Laronidase will be given by intravenous infusion (IV) through a catheter and from there to your child's body's cells and organs to break down the glycosaminoglycans (GAG) buildup.

Prior to starting ERT, subjects will have a complete physical examination, which includes a complete assessment of your child's airway and lungs. In addition to standard treatment evaluations and tests, which are done prior to hematopoietic stem cell transplant (HSCT), subjects will have the following tests: an additional teaspoon of blood for a baseline test for serum antibodies against laronidase, before and after the fourth dose of laronidase, the investigators will collect 2 teaspoons of blood for an alpha-L-iduronidase enzyme level; to watch for side effects to laronidase and the development of antibodies to laronidase, approximately 2 teaspoons of blood will be collected every 3 weeks while the subject is receiving laronidase ERT.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with the diagnosis of mucopolysaccharidosis type IH (MPS I, Hurler syndrome) who are candidates for first hematopoietic stem cell transplant (HSCT) according to a University of Minnesota myeloablative HSCT protocol.

Exclusion Criteria:

• Not being considered for University of Minnesota myeloablative HSCT protocol.
• Previous administration of laronidase enzyme
• Second or subsequent HSCT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laronidase ERT Treatment; Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant.	Procedure: Stem Cell Transplant; enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following; Other Names: ERT; Drug: Laronidase ERT; Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following.; Other Names: Aldurazyme®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients Alive at One Year Post Transplant	one year
Number of Patients Requiring Ventilator Support at One Year Post Transplant	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor Engraftment		Day 100 post transplant
Patients With Grade III-IV Acute GVHD		Day 100 post transplant
Reduction in Glycosaminoglycans (GAG)	Data was not collected on this outcome measure and is not available for reporting.	Prior to, During and After ERT
Toxicity (Adverse Events) Associated With Infusions of Laronidase	Data was not collected on this outcome measure and is not available for reporting.	1 year post transplant
Development of Anti-iduronidase Antibodies in Serum		1 Year
Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography		Baseline, 12 weeks after laronidase, after transplant

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Stem cell transplant; inborn errors of metabolism; Laronidase ERT; storage disease; hurler syndrome; glycosaminoglycans; enzyme replacement
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: MT2004-09; 0403M57728 (Other Identifier: IRB, University of Minnesota)