Clinical trial NCT00176891: Stem Cell Transplant w/Laronidase for Hurler
Official title: Phase II Study of Combined Laronidase (AldurazymeTM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mucopolysaccharidosis I
Hurler Syndrome
Keywords: Laronidase ERT
Stem cell transplant
storage disease
inborn errors of metabolism
hurler syndrome
glycosaminoglycans
enzyme replacement
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 25
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients Alive at One Year Post Transplant
timeFrame: one year
measure: Number of Patients Requiring Ventilator Support at One Year Post Transplant
timeFrame: one year
Secondary outcomes:
measure: Donor Engraftment
timeFrame: Day 100 post transplant
measure: Patients With Grade III-IV Acute GVHD
timeFrame: Day 100 post transplant
measure: Reduction in Glycosaminoglycans (GAG)
timeFrame: Prior to, During and After ERT
measure: Toxicity (Adverse Events) Associated With Infusions of Laronidase
timeFrame: 1 year post transplant
measure: Development of Anti-iduronidase Antibodies in Serum
timeFrame: 1 Year
measure: Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography
timeFrame: Baseline, 12 weeks after laronidase, after transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, MD
role: PRINCIPAL_INVESTIGATOR
References: