NCT04573140

A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)

A Phase I/II Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM), and Recurrent/Progressive Medulloblastoma (MB)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 4 Years
• Healthy volunteers: Not accepted

Summary

The primary objective will be to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in (Stratum 1) adult patients with newly diagnosed GBM (MGMT low level or unmethylated in adults only) and (Stratum 2) in pediatric patients with newly diagnosed HGG (pHGG). Funding Source - FDA OOPD

Detailed description

This is a first in human Phase I study of RNA-LP vaccines for newly diagnosed adult MGMT unmethylated (low level or undetected) glioblastoma (GBM) and pediatric patients with newly diagnosed HGG (pHGG). The phase I portion of the study will involve a dose-escalation study to identify the maximally tolerated dose (MTD). The GBM portion of the study is single site (UF) and the pediatric portion will be multisite. This clinical trial will consist of three parts: Surgery, Radiation, and Immunotherapy. Surgery and chemoradiation will be standard of care for patients with GBM. Potentially eligible participants will be enrolled on a screening consent for the sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs). Pediatric participants will have tumor material sent to the University of Florida (UF) from qualified PNOC sites. Adult GBM participants must have surgery for collection of tumor material at the University of Florida. Following surgical resection with confirmatory pathologic diagnosis, patients will be enrolled in the trial after informed consent has been obtained. The RNA-LP vaccination will begin within 4 weeks following radiation and after review of post-radiation MRI (for baseline). After radiation patients will receive three RNA-LP vaccines every 2 weeks before beginning 12 cycles of adjuvant monthly RNA- LP vaccines for a total of 15 vaccines. Participants may receive RNA-LP vaccines for up to 14 months. Participants will be followed until death due to any cause. MRI and clinical evaluation for assessment of disease progression will be conducted every 3 months for the first-year post-immunotherapy and then every 6-12 months over the next 2 years.

Conditions

• Adult Glioblastoma
• High Grade Glioma
• WHO Grade III or IV Malignant Glioma

Interventions

Type	Name	Description
BIOLOGICAL	Autologous total tumor mRNA and pp65 full length (fl) lysosomal associated membrane protein (LAMP) mRNA loaded DOTAP liposome vaccine administered intravenously (RNA loaded lipid particles, RNA-LPs)	RNA-LP vaccines will be administered intravenous. Three RNA-LP vaccines will be administered every 2 weeks followed by 12 cycles of adjuvant monthly RNA-LP vaccines for a total of 15 vaccines.

Timeline

• Start date: 2021-12-13
• Primary completion: 2027-07-01
• Completion: 2029-07-01
• First posted: 2020-10-05
• Last updated: 2026-03-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study