RNA-lipid Particle (RNA-LP) Vaccines for Recurrent/Progressive Medulloblastoma (MB)
ConditionRecurrent Medulloblastoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age4-39
SponsorUniversity of Florida
About this trial
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)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
Diffuse intrinsic pontine glioma, brainstem diffuse midline glioma, or BRAFV600E+
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)
Trial design
Design model
Single group
Treatments tested in this trial
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/VaccineRNA-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.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: recurrent/progressive Medulloblastoma (rMB)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
from the date of surgery until administration of third vaccine, up to 15 weeks2
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.
Time frame
First vaccine through 14 days after administration of the 3rd vaccine3
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.
Time frame
up to 60 monthsSponsors and contacts
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University of Florida
Lead sponsor
Pediatric Neuro-Oncology Consortium
Collaborator
Source ClinicalTrials.gov