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

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04284254
Collaborator
(none)
36
Enrollment
2
Arms
6
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Autologous Plasmablasts
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Sleeping Beauty Transposon-Engineered Plasmablasts for Expression and Delivery of Alpha-L-iduronidase in Patients With Hurler Syndrome That Have Previously Undergone Allogeneic Transplantation
Anticipated Study Start Date :
Dec 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: Dose Escalation

Drug: Autologous 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
Other Names:
  • Sleeping Beauty

    		•
    Experimental: Phase 2 - Expansion at MTD

    Drug: Autologous 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
    Other Names:
  • Sleeping Beauty

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    3. Safety and Tolerability after Infusion: Incidence of Adverse Events [1 Year]

      Incidence of Adverse Events

    Secondary Outcome Measures

    1. Z-score Growth Rate [1 Year]

      Estimate the 1-year Z-score growth rate standardized for age and gender

    2. Donor Engraftment [Baseline, 6 months and 1 Year]

      Estimate percent myeloid donor chimerism (CD33/66b) at baseline and at 6 and 12 months.

    3. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 8 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Principal Investigator: Paul Orchard, MD, University of Minnesota, Department of Pediatrics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT04284254
    Other Study ID Numbers:
    • 2018LS094
    • MT2018-18
    First Posted:
    Feb 25, 2020
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Masonic Cancer Center, University of Minnesota
    MPS IH
    Hurler syndrome
    Additional relevant MeSH terms:
    Mucopolysaccharidoses
    Mucopolysaccharidosis I
    Syndrome

    Study Results

    No Results Posted as of Apr 5, 2022