Stem Cell Transplant w/Laronidase for Hurler
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.
Procedure: Stem Cell Transplant
Drug: Laronidase ERT
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Combined Laronidase (AldurazymeTM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH)|
- Survival at one year and the proportion of patients in need of ventilator support by one year [ Time Frame: one year ] [ Designated as safety issue: No ]
- Donor engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
- Patients with Grade III-IV acute GVHD [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
- Reduction in glycosaminoglycans (GAG) [ Time Frame: Prior to, During and After ERT ] [ Designated as safety issue: No ]
- Toxicity (adverse events) associated with infusions of enzyme [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Development of anti-iduronidase antibodies in serum [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- Patients with Improvement in Obstructive Apnea (Breathing) by Polysomnography [ Time Frame: Baseline, 12 weeks after ERT, after transplant ] [ Designated as safety issue: No ]
|Study Start Date:||March 2004|
|Estimated Study Completion Date:||October 2013|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Laronidase 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 Name: ERTDrug: Laronidase ERT
10-12 weeks prior to HSCT, 8 weeks following
Other Name: Aldurazyme®
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.
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Paul Orchard, MD||Masonic Cancer Center, University of Minnesota|