The purpose of this research study is to learn about the safety and feasibility of giving a
personalized DNA vaccine to people with brain tumors that have returned or have been
resistant to treatment.
- Any patient ≤ 39 years of age who was diagnosed with a pediatric brain tumor of any
histologic subtype, who has now developed recurrent or refractory disease.
- Eligible to receive vaccine injections by TDS-IM electroporation device.
- Availability of tissue for sequencing to determine presence of targetable neoantigen.
This may be fresh tissue collected as part of routine care, another research project
or archived tissue from a previous craniotomy with biopsy, subtotal resection, total
gross resection, or re-resection.
- Karnofsky/Lansky performance status ≥ 60%
Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal
- Systemic corticosteroid therapy is permitted provided dosing is minimal based on
age 0.1mg/kg/day with a max of 4mg daily (dexamethasone or equivalent) on the day
of vaccine administration.
- Bevacizumab will be allowed if given for symptomatic control of vasogenic edema
and to avoid high dose of corticosteroids at the discretion of the treating
- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry
and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed
consent document (or that of legally authorized representative, if applicable).
- As this is a safety and feasibility study, prior immunotherapy will be permitted.
However, any prior immunotherapy must be discontinued at least 2 weeks before vaccine
administration. Non-immunologic therapy may be continued.
- No candidate neoantigen identified during screening.
- A history of other malignancy ≤ 3 years previous with the exception of non-melanoma
skin cancer, any in situ cancer that has been successfully resected and cured, treated
superficial bladder cancer, or any early-stage solid tumor that was successfully
resected without need for adjuvant radiation or chemotherapy.
- Currently receiving any other investigational agents.
- Known allergy, or history of serious adverse reaction to, vaccines such as
anaphylaxis, hives, or respiratory difficulty.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- History of pre-existing immunodeficiency disorder, autoimmune condition requiring
immunosuppressive therapy, or chronic infection (i.e. hepatitis B, hepatitis C, HIV).
This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease,
systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia,
immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus,
Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical
condition or use of medication which might make it difficult for the patient to
complete the full course of treatments or to generate an immune response to vaccines.
- Presence of clinically significant increased intracranial pressure (e.g. impending
herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of first dose of vaccine.
- Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
- Individuals in whom the ability to observe possible local reactions at the eligible
injection sites (deltoid region) is, in the opinion of the investigator, unacceptably
obscured due to a physical condition or permanent body art.
- Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or
hepatic or renal functional abnormality as determined by the investigator based on
medical history, physical examination, EKG, and/or laboratory screening test.
- Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
a single febrile seizure as a child.
- Syncopal episode within 12 months of screening.
- Current use of any electronic stimulation device, such as cardiac demand pacemakers,
automatic implantable cardiac defibrillator, nerve stimulators, or deep brain