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

• ClinicalTrials.gov Identifier: NCT04284254
• Recruitment Status: Withdrawn
• First Posted: February 25, 2020
• Last Update Posted: October 7, 2022
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Tracking Information

• First Submitted Date: November 11, 2019
• First Posted Date: February 25, 2020
• Last Update Posted Date: October 7, 2022
• Estimated Study Start Date: December 2022
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 24, 2020)

• 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
• 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
• Safety and Tolerability after Infusion: Incidence of Adverse Events [ Time Frame: 1 Year ]
  Incidence of Adverse Events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 24, 2020)

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

Original Secondary Outcome Measures (submitted: February 24, 2020)

• Z-score Growth Rate [ Time Frame: 1 Year ]
  Estimate the 1-year Z-score growth rate standardized for age and gender
• Donor Engraftment [ Time Frame: 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) [ Time Frame: 1 Year ]
  Determine levels of circulating antibodies (IgG, IgM, IgA and IgE) at baseline and at scheduled time points post infusion.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: Phase 1: Dose Escalation
  Intervention: Drug: Autologous Plasmablasts
• Experimental: Phase 2 - Expansion at MTD
  Intervention: Drug: Autologous Plasmablasts

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: October 5, 2022): 0
• Original Estimated Enrollment (submitted: February 24, 2020): 36
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 8 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04284254
• Other Study ID Numbers: 2018LS094; MT2018-18 ( Other Identifier: University of Minnesota Masonic Cancer Center )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Masonic Cancer Center, University of Minnesota
• Original Responsible Party: Same as current
• Current Study Sponsor: Masonic Cancer Center, University of Minnesota
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Masonic Cancer Center, University of Minnesota
• Verification Date: October 2022