Laronidase (Aldurazyme TM) Enzyme Replacement Therapy With Hematopoietic Stem Cell Transplant for Hurler Syndrome

Study Overview
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Brief Summary
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This is a standard of care treatment guideline for patients with the diagnosis of mucopolysaccharidosis type IH (MPS I, Hurler syndrome) who are being considered as candidates for first hematopoietic stem cell transplantation (HSCT) according to a University of Minnesota myeloablative HSCT protocol.

Detailed Description
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Laronidase Enzyme Replacement Therapy will be performed using laronidase once a week for 12 weeks prior to hematopoietic stem cell transplantation and for 8 weeks post-transplant to reduce pulmonary complications.

Official Title
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MT2011-21C Laronidase (Aldurazyme TM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH).

Conditions
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Mucopolysaccharidosis Type IH, MPS I, Hurler Syndrome

Intervention / Treatment
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* Drug: Laronidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of mucopolysaccharidosis type IH (MPS I, Hurler syndrome) and being considered as a candidate for first transplant according to a University of Minnesota myeloablative hematopoietic stem cell transplant (HSCT) protocol Exclusion Criteria: No prior therapy with laronidase enzyme replacement therapy (ERT)
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Laronidase use in Hurler Syndrome<br>Laronidase receiving prior and post transplant | Drug: Laronidase<br>* Administered 0.58 mg/kg/dose intravenously (IV) once a week beginning 12 weeks before planned hematopoietic stem cell transplant (HSCT) and resume same dosing regimen for 8 weeks after HSCT.<br>* Other names: Aldurazyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Patients alive at 1 year post transplantation. | At 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Engraftment | The incidence of donor engraftment will be estimated by taking the simple proportion of patients achieving donor engraftment over the number of evaluable patients. Donor engraftment will be defined as achieving an absolute neutrophil count ≥ 5x10^8/kg for three consecutive days before day 42 and maintenance of >10% donor chimerism through one year post transplant or death. | 1 Year Post Transplant | 
| Incidence of Grade III-IV Acute Graft Versus Host Disease | Cumulative incidence will be used to estimate grade III-IV acute GvHD, treating death as a competing risk. | Day 100 | 
| Proportion of patients in need of ventilator support | Count of patients using ventilator by 1 year. | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hurler Syndrome