RNA-lipid Particle (RNA-LP) Vaccines for Recurrent/Progressive Medulloblastoma (MB) (PNOC020 rMB)

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)

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 pediatric patients with recurrent/progressive Medulloblastoma (MB)

Study Overview

• Status: Recruiting
• Conditions: Recurrent Medulloblastoma
• Intervention / Treatment: 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)

Detailed Description

This is a first in human Phase I study of RNA-LP vaccines for pediatric patients with recurrent/progressive Medulloblastoma (MB). The phase I portion of the study will involve a dose-escalation study to identify the maximally tolerated dose (MTD).

This clinical trial will consist of three parts: Surgery, Salvage Therapy (Radiation and/or chemotherapy), and Immunotherapy. 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. 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 salvage therapy 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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Elias Sayour, MD, PhD; Phone Number: 352-273-9000; Email: Wells-BTC@ufl.edu
• Study Contact Backup: Name: Jannerfer An; Phone Number: (415) 476-3831; Email: PNOC020@ucsf.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Recruiting
      • UF Health Shands Children's Hospital
      • Principal Investigator: John Ligon, MD
      • Contact: Marcia Hodik, RN; Phone Number: 352-273-9000; Email: Wells-BTC@ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 3 and </= 39 years.
• Histologically confirmed or suspected recurrent/progressive MB in first or second relapse.
• Patients must have received radiation therapy as part of prior therapy.
• Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).

• Prior Therapy: Patients must have fully recovered from all acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.

  • XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis.
  • Other therapeutic clinical trials: ≥ 14 days after last dose of investigational agent, unless otherwise defined above.
  • Patients must not have received prior exposure to pp65-directed therapy or any RNA-LP therapy.
• A diagnostic contrast-enhanced MRI of the brain and spine must be performed preoperatively, and diagnostic contrast-enhanced MRI of the area biopsied or resected must be performed postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment. Post-op MRI must be completed within 7 days after surgery.
• Performance Score: Karnofsky ≥ 60 for participants > 16 years of age and Lansky ≥ 60 for participants < 16 years of age (See Appendix A) assessed within 2 weeks prior to enrollment. 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:

  d. ANC (Absolute neutrophil count) ≥ 1,000/μl (unsupported) e. Platelets ≥ 100/μl (unsupported for at least 7 days) f. Hemoglobin > 8 g/dL (may be supported)

• Renal: Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2

• Hepatic:

  d. Bilirubin ≤ 3 times upper limit of institutional normal for age. e. SGPT (ALT) ≤ 5 times upper limit of institutional normal for age. f. SGOT (AST) ≤ 5 times upper limit of institutional normal for age.

• Participants who are receiving systemically-administered steroids must be on a stable or decreasing dose for >1 week prior to enrollment. The patient steroid dose should be no more than a dexamethasone-equivalent of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.
• Willing to take an antiepileptic medication such as levetiracetam for the duration of RNA-LP vaccinations
• A legal parent/guardian or patient must be able to understand and be willing to sign a written informed consent document
• 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 of child-fathering 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.
• Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.
• Patients must be enrolled on PNOC COMP prior to enrollment on PNOC020 if PNOC COMP is open to accrual at the enrolling institution.

Exclusion Criteria:

• Diffuse intrinsic pontine glioma, brainstem diffuse midline glioma, or BRAFV600E+

• Bulky disease, defined as:

  • Tumor with evidence of clinically significant uncal herniation, midline shift, tonsillar herniation, or brainstem infiltration, or that shows significant mass effect in either brain or spine
  • Tumor with extensive and diffuse multilobular involvement (>3 lobes)
  • Tumor with extracranial disease (with the exception of spinal metastases in Stratum 3)
• Known HIV, Hepatitis B, or Hepatitis C seropositive.
• Uncontrolled seizure disorder
• History of myocarditis
• Receipt of any live vaccine within 30 days prior to enrollment
• Known active infection or immunosuppressive disease.
• Participants with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.
• Severe or unstable concurrent medical conditions.
• Women 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 study entry.
• Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: recurrent/progressive Medulloblastoma (rMB)

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Manufacturing feasibility	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 administration of third vaccine, up to 15 weeks
Safety of RNA-LP vaccine	Number of patients with DLTs at MTD. DLTs will be monitored for two weeks after the 3rd vaccine before continuing with the next dose escalation. If there are no DLTs, only patients receiving at least 3 vaccines without toxicity will be considered as safe for MTD assessment. Patients receiving less than 3 vaccines will be replaced for safety MTD assessments. Toxicity encountered before the 3rd vaccine will be considered a DLT. If 2 or more DLTs are observed at any dose level, the dose level is determined to be unsafe, and no additional patients will be treated at that level and there will be no escalation beyond that level.	First vaccine through 14 days after administration of the 3rd vaccine
Determination of Maximum Tolerated Dose	A traditional 3+3 phase 1 design will be employed during this study, where dose escalations are planned in groups of three patients. No intra-patient escalation will be allowed, and dose escalation will not be considered until toxicity information is available from at least 3 evaluable patients at the current dose level.	up to 60 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Pediatric Neuro-Oncology Consortium
• Investigators: Study Chair: Sabine Mueller, MD, PhD, University of California, San Francisco; Principal Investigator: Elias Sayour, MD, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Membrane Proteins; Glycoproteins; Glycoconjugates; Membrane Glycoproteins; Lysosomal Membrane Proteins
• Other Study ID Numbers: IRB202001710-rMB; CC#200813 (Other Identifier: PNOC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No