Hurler Syndrome, Mucopolysaccharidosis I
Conditions
Keywords
Laronidase ERT, Stem cell transplant, storage disease, inborn errors of metabolism, hurler syndrome, glycosaminoglycans, enzyme replacement
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.
Interventions
PROCEDUREStem Cell Transplant
enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following
DRUGLaronidase ERT
Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 7 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Glycosaminoglycans (GAG) | Prior to, During and After ERT | Data was not collected on this outcome measure and is not available for reporting. |
| Toxicity (Adverse Events) Associated With Infusions of Laronidase | 1 year post transplant | Data was not collected on this outcome measure and is not available for reporting. |
| Donor Engraftment | Day 100 post transplant | — |
| Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography | Baseline, 12 weeks after laronidase, after transplant | — |
| Development of Anti-iduronidase Antibodies in Serum | 1 Year | — |
| Patients With Grade III-IV Acute GVHD | Day 100 post transplant | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Laronidase ERT Treatment Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant.
Stem Cell Transplant: enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following
Laronidase ERT: Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Laronidase ERT Treatment |
|---|---|
| Age, Categorical <=18 years | 22 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 22 |
| serious Total, serious adverse events | 6 / 22 |
Outcome results
Primary
Number of Patients Alive at One Year Post Transplant
Time frame: one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Laronidase ERT Treatment | Number of Patients Alive at One Year Post Transplant | 18 Participants |
Primary
Number of Patients Requiring Ventilator Support at One Year Post Transplant
Time frame: one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Laronidase ERT Treatment | Number of Patients Requiring Ventilator Support at One Year Post Transplant | 6 Participants |
Secondary
Development of Anti-iduronidase Antibodies in Serum
Time frame: 1 Year
Population: Data was not collected on this outcome measure and is not available for reporting.
Secondary
Donor Engraftment
Time frame: Day 100 post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Laronidase ERT Treatment | Donor Engraftment | 21 Participants |
Secondary
Patients With Grade III-IV Acute GVHD
Time frame: Day 100 post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Laronidase ERT Treatment | Patients With Grade III-IV Acute GVHD | 1 Participants |
Secondary
Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography
Time frame: Baseline, 12 weeks after laronidase, after transplant
Population: Data was not collected on this outcome measure and is not available for reporting.
Secondary
Reduction in Glycosaminoglycans (GAG)
Data was not collected on this outcome measure and is not available for reporting.
Time frame: Prior to, During and After ERT
Population: Data was not collected on this outcome measure and is not available for reporting.
Secondary
Toxicity (Adverse Events) Associated With Infusions of Laronidase
Data was not collected on this outcome measure and is not available for reporting.
Time frame: 1 year post transplant
Population: Data was not collected on this outcome measure and is not available for reporting.