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Withdrawn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
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
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
NCT ID
NCT04284254
First Posted
November 11, 2019
Last Updated
October 5, 2022
Sponsor
Masonic Cancer Center, University of Minnesota
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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