MPS IH, Hurler Syndrome, Mucopolysaccharidosis Type IH, Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome)
Conditions
Keywords
MPS IH, Hurler syndrome
Brief summary
This is a single center, Phase 1/2 study in which patients with Hurler syndrome who have previously undergone allogeneic hematopoietic stem cell transplantation are treated with autologous plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system.
Interventions
DRUGAutologous Plasmablasts
Autologous Plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system. Phase 1: * Dose Level 1: 5 x 10e7 cells/kg on Day 0 * Dose Level 2: 1 x 10e8 cells/kg on Day 0 * Dose Level 3: 1 x 10e8 cells/kg x 2 doses on Day 0 and Day 30 +/-3 days. Phase 2: \- Maximum Tolerated Dose (MTD) established in Phase I
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome) * Underwent a previous hematopoietic stem cell transplant \>1 year prior to study enrollment * Age ≥3 years and ≤8 years at time of study registration * ≥ 10 kilograms body weight * Creatinine \<1.5 normal for gender and age. * Ejection fraction ≥ 40% by echocardiogram * Must commit to traveling to the University of Minnesota for the necessary followup evaluations * Must agree to stay in the Twin Cities area (\<45-minute drive from the Masonic Children's Hospital) for a minimum of 5 days after each cell infusion * Voluntary written parental consent prior to the performance of any study related procedures
Exclusion criteria
* Prior enzyme replacement therapy within 4 months prior to enrolling on study * History of B cell related cancer, EBV lymphoproliferative disease or autoimmune disorders * Evidence of active graft vs. host disease * Requirement for systemic immune suppression * Requirement for continuous supplemental oxygen * Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment. * In the investigator's judgement, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 1 Year | Maximum tolerated dose (MTD) of autologous plasmablasts engineered to express large amounts of α-L-iduronidase (IDUA) using a Sleeping Beauty transposon approach |
| Growth Velocity (cm/year) | 1 Year | Growth velocity in centimeters/year over a one-year period through determinations of sitting and standing height at baseline and post infusion |
| Safety and Tolerability after Infusion: Incidence of Adverse Events | 1 Year | Incidence of Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Z-score Growth Rate | 1 Year | Estimate the 1-year Z-score growth rate standardized for age and gender |
| Donor Engraftment | Baseline, 6 months and 1 Year | Estimate percent myeloid donor chimerism (CD33/66b) at baseline and at 6 and 12 months. |
| Levels of circulating antibodies (IgG, IgM, IgA and IgE) | 1 Year | Determine levels of circulating antibodies (IgG, IgM, IgA and IgE) at baseline and at scheduled time points post infusion. |
Outcome results
None listed