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

NCT ID: NCT04284254

Last Updated: 2022-10-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-31
• Study Completion Date: 2023-06-30

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Dose Escalation

Group Type: EXPERIMENTAL

Autologous Plasmablasts

Intervention Type: DRUG

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

Phase 2 - Expansion at MTD

Group Type: EXPERIMENTAL

Autologous Plasmablasts

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Sleeping Beauty

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Orchard, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota, Department of Pediatrics

Other Identifiers

MT2018-18

Identifier Type: OTHER

Identifier Source: secondary_id

2018LS094

Identifier Type: -

Identifier Source: org_study_id