NCT04573140

Brief 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

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
38mo left

Started Dec 2021

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress58%
Dec 2021Jul 2029

First Submitted

Initial submission to the registry

September 14, 2020

Completed
21 days until next milestone

First Posted

Study publicly available on registry

October 5, 2020

Completed
1.2 years until next milestone

Study Start

First participant enrolled

December 13, 2021

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2027

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2029

Last Updated

April 24, 2026

Status Verified

April 1, 2026

Enrollment Period

5.6 years

First QC Date

September 14, 2020

Last Update Submit

April 22, 2026

Conditions

WHO Grade III or IV Malignant GliomaAdult GlioblastomaHigh Grade Glioma

Keywords

ImmunotherapyBrain TumorAdultnewly diagnosedclinical trialPediatric brain tumor

Outcome Measures

Primary Outcomes (3)

  • Manufacturing feasibility

    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). Tumor material will be sent to the University of Florida (UF) where tumor specific RNA-LP vaccines will be manufactured. Manufacturing feasibility will be determined based on the percentage of vaccines that are successfully manufactured in the DLT window during the first three vaccines. If two-thirds of vaccines are successfully manufactured with QA/QC clearance, we will conclude that RNA-LPs can be successfully manufactured.

    from the date of surgery until adminstration of third vaccine, up to 20 weeks

  • Safety of RNA-LP vaccine

    A DLT will be defined as any immunotherapy-related (possible, probable or definite): * Grade ≥ 3 non-hematologic toxicity that does not improve to ≤ Grade 2 within 72 hours; hepatic or renal dysfunction that does not improve to ≤ grade 2 within 7 days * Grade ≥3 cytokine release syndrome that does not improve to ≤ Grade 2 within 72 hours * Grade ≥ 3 encephalopathy as defined by the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Immune Effector Cell-Associated Encephalopathy criteriaGrade 3 or greater non-neurologic, non-hematologic toxicity * Grade 3 neurologic toxicity that does not improve to Grade II or better within 7 days * Grade 3-4 hematologic toxicity that does not improve to Grade 2 or better within 14 days * Grade 3 autoimmune encephalomyelitis * Grade 4 neurologic toxicity.

    First vaccine through 14 days after administration of the 3rd vaccine.

  • Determination of Maximum Tolerated Dose

    The Phase I Stratum 1 dose-escalation study will be performed in up to 28 adult participants using a Bayesian optimal interval (BOIN) design with an initial embedded accelerated titration design (ATD) to efficiently identify the maximally tolerated dose (MTD). For the initial ATD, patients will be enrolled and treated in cohorts of size 1 starting at dose level -4 to dose level -1. After the first DLT is observed or if dose level 0 is reached without prior DLT in dose level -4 to -1, the study will expand to a BOIN design with a cohort size of 3 to identify the MTD. For the initial ATD, patients will be enrolled and treated in cohorts of size 1 starting at dose level -4 to dose level -1, and will expand to a cohort size of 3 after the first DLT is observed or at dose level 0. There are 8 dose levels to potentially be assessed including the possibility of 4 dose levels for the ATD and 4 for the BOIN.

    up to 30 months

Study Arms (2)

Adult GBM (Stratum 1)

EXPERIMENTAL
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)

Pediatric HGG (Stratum 2)

EXPERIMENTAL
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)

Interventions

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)BIOLOGICAL

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.

Adult GBM (Stratum 1)Pediatric HGG (Stratum 2)

Eligibility Criteria

Age4 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

  • Stratum 1 (Adult GBM)
  • Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.)
  • MGMT Methylated tumors
  • Gliomatosis Cerebri
  • Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
  • Recurrent or multifocal malignant gliomas.
  • Metastatic or leptomeningeal disease
  • Residual post-surgical disease burden \> 3 cm as defined by longest perpendicular diameter on MRI.
  • Known HIV, Hepatitis B, or Hepatitis C seropositive.
  • Known active infection or immunosuppressive disease.
  • Participants who require corticosteroids above physiologic doses or not weaned to physiologic dosing within 1 week of scheduled vaccination.
  • Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region, other than TMZ prescribed during radiation for GBM (prior chemotherapy for a different cancer is allowable).
  • Prior radiotherapy to the head or neck, resulting in overlap of radiation fields. Radiosurgery is not permitted.
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization.
  • +28 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UF Health

Gainesville, Florida, 32610, United States

RECRUITING

Related Publications (3)

  • Carrera-Justiz S, Aghaee M, Qdaisat S, Weidert F, Garcia GA, Fagman L, Zhang D, Stover B, Moor RSF, Xie C, Goldenberg E, von Roemeling C, Doonan B, Chardon-Robles J, Elliott L, Sawyer WG, Deleyrolle LP, Sahay B, Foster TP, Seligson ND, Rahman M, Ghiaseddin A, Castillo P, Lee JH, Silver NL, Doty A, Ligon JA, Milner RJ, Mitchell D, Mendez-Gomez H, Moore H, Sayour EJ. Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors. J Immunother Cancer. 2025 Nov 11;13(11):e011817. doi: 10.1136/jitc-2025-011817.

    PMID: 41218853DERIVED

  • Villanueva MT. RNA delivery heats up cold tumours. Nat Rev Drug Discov. 2024 Jul;23(7):497. doi: 10.1038/d41573-024-00098-0. No abstract available.

    PMID: 38858569DERIVED

  • Melnick K, Dastmalchi F, Mitchell D, Rahman M, Sayour EJ. Contemporary RNA Therapeutics for Glioblastoma. Neuromolecular Med. 2022 Mar;24(1):8-12. doi: 10.1007/s12017-021-08669-9. Epub 2021 Jun 8.

    PMID: 34101090DERIVED

MeSH Terms

Conditions

GlioblastomaGliomaLymphoma, FollicularBrain Neoplasms

Interventions

Lysosomal Membrane Proteins

Condition Hierarchy (Ancestors)

AstrocytomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueLymphoma, Non-HodgkinLymphomaLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Membrane GlycoproteinsGlycoproteinsGlycoconjugatesCarbohydratesProteinsAmino Acids, Peptides, and ProteinsMembrane Proteins

Study Officials

  • Elias Sayour, MD, PhD

    University of Florida

    STUDY CHAIR

Central Study Contacts

Marcia Hodik

CONTACT

352-273-5519wells-BTC@ufl.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 14, 2020

First Posted

October 5, 2020

Study Start

December 13, 2021

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2029

Last Updated

April 24, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)