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

Phase 1

Withdrawn

• Conditions: Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome); Mucopolysaccharidosis Type IH; MPS IH, Hurler Syndrome
• Interventions: Drug: Autologous Plasmablasts

• Registration Number: NCT04284254
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-11
• Study First Submitted QC: 2020-02-24
• Study First Posted: 2020-02-25
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-05
• Last Update Posted: 2022-10-07
• Study Start: 2022-12
• Primary Completion: 2023-06
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2 - Expansion at MTD	Autologous Plasmablasts	-
Phase 1: Dose Escalation	Autologous Plasmablasts	-

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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.