MT2018-18: Sleeping Beauty Transposon-Engineered Plasmablasts for Hurler Syndrome Post Allo HSCT

study id #: NCT04284254

condition: Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome), Mucopolysaccharidosis Type IH, MPS IH, Hurler Syndrome

status: Not yet recruiting

purpose:

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.

intervention: Autologous Plasmablasts

results: https://clinicaltrials.gov/ct2/show/results/NCT04284254

last updated: February 26, 2022

start date: December 2021

estimated completion: June 2023

last updated: July 8, 2021

phase of development: Phase 1/Phase 2

size / enrollment: 36

primary outcomes:

• Maximum Tolerated Dose (MTD)
  Maximum tolerated dose (MTD) of autologous plasmablasts engineered to express large amounts of α-L-iduronidase (IDUA) using a Sleeping Beauty transposon approach
• 1 Year
  Growth Velocity (cm/year)
  Growth velocity in centimeters/year over a one-year period through determinations of sitting and standing height at baseline and post infusion
• 1 Year
  Safety and Tolerability after Infusion: Incidence of Adverse Events
  Incidence of Adverse Events
• 1 Year
  

secondary outcomes:

• Z-score Growth Rate
  1 Year
• Donor Engraftment
  Baseline, 6 months and 1 Year
• Levels of circulating antibodies (IgG, IgM, IgA and IgE)
  1 Year

inclusion criteria:

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: 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.

sponsor: Masonic Cancer Center, University of Minnesota

contacts: Paul Orchard, MD, (612)-626-2313, orcha001@umn.edu

investigators: Paul Orchard, MD,University Of Minnesota, Department Of Pediatrics

trial center locations: