A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)

Exclusion Criteria

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.
  • Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at initiation of XRT/TMZ.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at initiation of XRT/TMZ.
  • 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.
  • Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity.
  • 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.

• Prior history of brachial neuritis or Guillain-Barré syndrome.

• 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

Stratum 2 (Pediatric HGG)

• Diffuse intrinsic pontine glioma, brainstem diffuse midline glioma, or BRAFV600E+
• Gliomatosis
• Metastatic or leptomeningeal disease
• Residual post-surgical disease burden > 3 cm as defined by longest diameter on MRI.
• 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.
• Participants who are anticipated to require corticosteroids above physiologic doses or not weaned to physiologic dosing within 1 week of scheduled vaccination.
• 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.