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

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ClinicalTrials.gov Identifier: NCT04284254
Recruitment Status : Withdrawn (Study went on hold because more pre-clinical work needs to be done per FDA feedback.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.)
First Posted : February 25, 2020
Last Update Posted : October 7, 2022
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Description
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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
Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome) Mucopolysaccharidosis Type IH MPS IH, Hurler Syndrome Drug: Autologous Plasmablasts Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 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
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Sleeping Beauty


Outcome Measures
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Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 1 Year ]
    Incidence of Adverse Events


Secondary Outcome Measures :
  1. Z-score Growth Rate [ Time Frame: 1 Year ]
    Estimate the 1-year Z-score growth rate standardized for age and gender

  2. Donor Engraftment [ Time Frame: 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) [ Time Frame: 1 Year ]
    Determine levels of circulating antibodies (IgG, IgM, IgA and IgE) at baseline and at scheduled time points post infusion.


Eligibility Criteria
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Ages Eligible for Study:   3 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04284254


Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Paul Orchard, MD University of Minnesota, Department of Pediatrics
More Information
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT04284254    
Other Study ID Numbers: 2018LS094
MT2018-18 ( Other Identifier: University of Minnesota Masonic Cancer Center )
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: October 7, 2022
Last Verified: October 2022

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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:
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Mucopolysaccharidoses
Mucopolysaccharidosis I
Syndrome
Disease
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
 Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases