Recruiting
Phase 1

RNA-LP Vaccines

Sponsor:

University of Florida

Code:

NCT06389591

Conditions

Recurrent Glioblastoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1)

RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2)

Study Details

Brief summary:

This is a Phase I study to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in adult patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma

Study ID

NCT06389591

Start date

Dec 2, 2024

Status verified date

May, 2026

Completion date

Dec 1, 2027

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age >/= 18years
  • Histopathologically proven GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).
  • Unequivocal evidence of tumor progression as documented by brain MRI scan per RANO criteria.
  • Tumor must have a primary supratentorial component at the time of disease progression.
  • Patients must have received surgery and completed Fractionated Radiation therapy as frontline treatment for primary disease, either alone or with concurrent therapy (including temozolomide or another systemic chemotherapy agent). Patients must be at least 12 weeks post chemoradiation completion.
  • Patient must be at least 90 days from completion of prior radiation
  • Any adverse events patient has experienced from prior therapy must have resolved to ≤ Gr. 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) v5.0 prior to enrollment
  • Patient must be either weaned off steroids or weaned onto physiologic dosing at the time of enrollment.
  • Patient must be a candidate for surgery/biopsy as acceptable standard of care for sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).
  • A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.
  • Performance Score: (KPS) ≥ 60. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Bone Marrow:

  • ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported)
  • Platelets ≥ 100/µl (unsupported for at least 3 days)
  • Hemoglobin > 8 g/dL
  • Renal:

  • BUN ≤ 25 mg/dl
  • Creatinine ≤ 1.7 mg/dl
  • Hepatic

  • Bilirubin ≤ 2.0 mg/dl
  • ALT ≤ 5 times institutional upper limits of normal for age
  • AST ≤ 5 times institutional upper limits of normal for age
  • Patient must be able to give consent.
  • For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment.
  • WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
  • Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

Exclusion Criteria:

  • Patients who received prior treatment with bevacizumab.
  • Known active infection (requiring treatment by antiviral or antibiotics) or immunosuppressive disease.
  • Patients with multifocal recurrent disease characterized by more than one enhancing lesion separated by noncontiguous T2/FLAIR signal abnormality. Patients with recurrence outside of the original tumor site are eligible if there is stability at the original site of disease.
  • Patients with uncontrolled seizure disorders
  • Any patients that have received any live vaccines within 30 days prior to enrollment
  • Tumors with primary localization to the brainstem or spinal cord
  • Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization.
  • Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.
  • Acute bacterial or fungal infection requiring intravenous treatment at study treatment.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at study treatment
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
  • Patients with autoimmune disease requiring medical management with immunosuppressants.
  • Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
  • Pregnancy or women of childbearing potential and men who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • Women of childbearing potential must not be pregnant or breast-feeding.
  • Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to projected first dose of study treatment.
  • Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: pp65 RNA-LPs (DP1) before biopsy

Participants will receive pp65 RNA-LPs (DP1) starting before tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Interventions

pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1)

pp65 RNA loaded lipid particles or pp65 RNA-LPs administered intravenously

RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2)

personalized tumor mRNA, pp65 fl LAMP mRNA and DOTAP liposomes or RNA loaded lipid particles, RNA-LPs administered intravenously

Primary outcome measure

  • Percentage of vaccines meeting release criteria in the DLT window during the first three vaccines [ Time Frame: from the date of surgery until administration of third vaccine, up to 20 weeks ]
  • Incidence of investigational treatment related toxicities [ Time Frame: from first vaccine to 30 days after last dose of vaccine administered, up to 17 months ]

Central Contacts and Locations

Central contacts

Phuong Deleyrolle

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

Locations

UF Health

Recruiting

Gainesville, Florida, United States, 32608

Contacts

Phuong Deleyrolle

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

Principal Investigator:

Ashley Ghiaseddin, MD

More Information

Sponsor

University of Florida

Last update posted

May 15, 2026

Last verified

May, 2026

Keywords

  • brain tumor
  • malignant brain tumor
  • immunotherapy
  • adult

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Florida on 2026-05-15.