Stem Cell Transplant w/Laronidase for Hurler

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Mucopolysaccharidosis I, Hurler Syndrome

Intervention / Treatment
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* Procedure: Stem Cell Transplant
* Drug: Laronidase ERT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Laronidase ERT, Stem cell transplant, storage disease, inborn errors of metabolism, hurler syndrome, glycosaminoglycans, enzyme replacement