Stem Cell Transplant w/Laronidase for Hurler

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00176891
First received: September 12, 2005
Last updated: July 8, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Mucopolysaccharidosis I
Hurler Syndrome
Procedure: Stem Cell Transplant
Drug: Laronidase ERT
Phase 2

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 25
Study Start Date: March 2004
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ERT
Drug: Laronidase ERT
Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following.
Other Name: Aldurazyme®

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

Ages Eligible for Study:   up to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176891

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00176891     History of Changes
Other Study ID Numbers: MT2004-09, 0403M57728
Study First Received: September 12, 2005
Last Updated: July 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
Laronidase ERT
Stem cell transplant
storage disease
inborn errors of metabolism
hurler syndrome
glycosaminoglycans
enzyme replacement

Additional relevant MeSH terms:
Mucopolysaccharidosis I
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on August 19, 2014