Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

Masonic Cancer Center, University of Minnesota11 enrolled

Overview

This is a single center pilot study in which Laronidase will be given weekly for two years in patients with Hurler syndrome, also known as mucopolysaccharide IH (MPS I, Hurler syndrome), that have previously been treated with an allogeneic transplant.

This 2-year open-label pilot study of laronidase includes patients (age 5-13 years) who are at least 2 years post-hematopoietic cell transplantation (HCT) and donor engrafted. Outcomes are assessed semi-annually and compared to historic controls. Eligible patients will receive Laronidase as an infusion over several hours once a week at a local site. The dosing of enzyme will be the standard doses recommended by Genzyme. The findings of this Pilot Study will be used to assess whether a subsequent larger study can be conducted.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hurler Syndrome

Interventions

LaronidaseDRUG

Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years

Eligibility

Sex: ALLMax age: 14 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously * Age \<14 years old * \>10% engrafted based on recent testing (\<4 months prior to enrollment) * Willing to commit to traveling to the University of Minnesota every 6 months * Written informed consent prior to the performance of any study related procedures Exclusion Criteria: * Previous administration of Laronidase enzyme \> 3 months post transplantation * Anticipated survival less than 2 years * History of cardiac or pulmonary insufficiency, including an ejection fraction (EF) \< 40% or those requiring continuous supplemental oxygen

Locations (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Outcomes

Primary Outcomes

Percentage of Adherence to the Scheduled Weekly Infusion by the Participants

To determine the feasibility of giving weekly Laronidase for 2 years in patients with Hurler syndrome after allogeneic transplantation, compliance throughout the study with drug administration, the percentage of adherence to the scheduled weekly infusion for each participant is measured.

Time frame: 24 months

Number of Participants Experiencing Severe Adverse Events

Number of participants experiencing severe adverse events that occur after administration with Laronidase to determine the feasibility of giving weekly Laronidase

Time frame: 24 months

Secondary Outcomes

Changes in Growth Velocity

difference between baseline and month 24 growth velocities

Time frame: Baseline, Month 24

Change in Muscle Strength

Handgrip strength is measured three times in both hands with a mechanical handheld Biodex System 3 dynamometer (Biodex medical Systems, Inc., Shirley, NY) with the subject in a seated position at each visit; the average for each hand is presented.

Time frame: Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

Change in Peak Heart Rate to Monitor "Fitness"

A modified Balke Treadmill Test was performed. Briefly, patients began walking at 2.0 mph with a 2% increase in grade every 2 min. A 12-lead electrocardiogram was monitored continuously throughout the test for the determination of heart rate and dysrhythmias or ischemic changes. Heart rate was measured at the end of each stage (i.e. every 2 min) .

Data from ClinicalTrials.gov

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Correlation of 6 Minute Walk Test With Anti-laronidase Antibody + Status

6 minute walk test (6MWT) was performed to assess overall physical function and health status. In brief, a 30m hospital corridor marked by colored tape at each end was used. Subjects were instructed to walk from end to end at their self-selected pace, while attempting to cover as much distance as possible in the 6 min. The patients were instructed to walk around the mark as they changed direction. The time and distance covered was recorded, as was the heart rate prior to and immediately after completion of the walk test. To find the association between the rate of change in 6MWT, and anti drug antibody (ADA) titer, a statistical test is performed adjusting for age at the time of enrollment.