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

Primary Purpose

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

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Autologous Plasmablasts
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome) focused on measuring MPS IH, Hurler syndrome

Eligibility Criteria

3 Years - 8 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Phase 1: Dose Escalation

    Phase 2 - Expansion at MTD

    Arm Description

    Outcomes

    Primary Outcome Measures

    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
    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
    Safety and Tolerability after Infusion: Incidence of Adverse Events
    Incidence of Adverse Events

    Secondary Outcome Measures

    Z-score Growth Rate
    Estimate the 1-year Z-score growth rate standardized for age and gender
    Donor Engraftment
    Estimate percent myeloid donor chimerism (CD33/66b) at baseline and at 6 and 12 months.
    Levels of circulating antibodies (IgG, IgM, IgA and IgE)
    Determine levels of circulating antibodies (IgG, IgM, IgA and IgE) at baseline and at scheduled time points post infusion.

    Full Information

    First Posted
    November 11, 2019
    Last Updated
    October 5, 2022
    Sponsor
    Masonic Cancer Center, University of Minnesota
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04284254
    Brief Title
    MT2018-18: Sleeping Beauty Transposon-Engineered Plasmablasts for Hurler Syndrome Post Allo HSCT
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2022
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study went on hold because more pre-clinical work needs to be done per FDA feedback. However, the study never went off hold and the study team has decided to close this study without opening to enrollment.
    Study Start Date
    December 2022 (Anticipated)
    Primary Completion Date
    June 2023 (Anticipated)
    Study Completion Date
    June 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Masonic Cancer Center, University of Minnesota

    4. Oversight

    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

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome), Mucopolysaccharidosis Type IH, MPS IH, Hurler Syndrome
    Keywords
    MPS IH, Hurler syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Phase 1: Dose Escalation
    Arm Type
    Experimental
    Arm Title
    Phase 2 - Expansion at MTD
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Autologous Plasmablasts
    Other Intervention Name(s)
    Sleeping Beauty
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Maximum Tolerated Dose (MTD)
    Description
    Maximum tolerated dose (MTD) of autologous plasmablasts engineered to express large amounts of α-L-iduronidase (IDUA) using a Sleeping Beauty transposon approach
    Time Frame
    1 Year
    Title
    Growth Velocity (cm/year)
    Description
    Growth velocity in centimeters/year over a one-year period through determinations of sitting and standing height at baseline and post infusion
    Time Frame
    1 Year
    Title
    Safety and Tolerability after Infusion: Incidence of Adverse Events
    Description
    Incidence of Adverse Events
    Time Frame
    1 Year
    Secondary Outcome Measure Information:
    Title
    Z-score Growth Rate
    Description
    Estimate the 1-year Z-score growth rate standardized for age and gender
    Time Frame
    1 Year
    Title
    Donor Engraftment
    Description
    Estimate percent myeloid donor chimerism (CD33/66b) at baseline and at 6 and 12 months.
    Time Frame
    Baseline, 6 months and 1 Year
    Title
    Levels of circulating antibodies (IgG, IgM, IgA and IgE)
    Description
    Determine levels of circulating antibodies (IgG, IgM, IgA and IgE) at baseline and at scheduled time points post infusion.
    Time Frame
    1 Year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    8 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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: 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Paul Orchard, MD
    Organizational Affiliation
    University of Minnesota, Department of Pediatrics
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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