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

NCT07492316 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB202001710-rMBCC#200813
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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 pediatric patients with recurrent/progressive Medulloblastoma (MB)

Conditions

Recurrent Medulloblastoma

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

recurrent/progressive Medulloblastoma (rMB)

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.

recurrent/progressive Medulloblastoma (rMB)

Eligibility Criteria

• Age: 4 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Pediatric Neuro-Oncology Consortium: collaborator

Study Sites (1)

UF Health Shands Children's Hospital

Gainesville, Florida, 32608, United States

RECRUITING

MeSH Terms

Conditions

Medulloblastoma

Interventions

Lysosomal Membrane Proteins

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins

Study Officials

• Sabine Mueller, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

• Elias Sayour, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elias Sayour, MD, PhD

CONTACT

352-273-9000; Wells-BTC@ufl.edu

Jannerfer An

CONTACT

(415) 476-3831; PNOC020@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 25, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): March 31, 2031
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)