Eligibility Criteria for Tissue Sequencing (Step 1)
Inclusion Criteria:
- - Any patient between the ages of 12 and 25 years of age (inclusive) who was diagnosed
with a pediatric brain tumor of any histologic subtype, who has now developed
recurrent or refractory disease.
- - All patients enrolled in this trial will receive standard of care treatment for
recurrent and/or refractory pediatric brain tumors, including systemic agents, prior
to receiving the investigational agent.
- - 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.
- - Ability to understand and willingness to sign an IRB approved written informed
consent document (or that of legally authorized representative, if applicable) or
patient has a guardian who has the ability to understand and willingness to sign an
IRB approved written informed consent document.
Eligibility Criteria for Treatment Administration (Step 2) Step 2 Inclusion Criteria.
- - Personalized neoantigen DNA vaccine manufactured for administration.
- - Karnofsky/Lansky performance status ≥ 60%
- Life expectancy > 24 weeks.
- - Prior therapy washout requirements (with exception of bevacizumab):
- Myelosuppressive chemotherapy: Participants must have received their last dose
of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to
first dose of vaccine (6 weeks prior if nitrosurea).
- - Biologic agent: Participant must have received their last dose of the biologic
agent no less than 7 days prior to first dose of vaccine.
- - For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended to beyond the time during
which adverse events are known to occur.
The duration of this interval
should be discussed with the study chair.
- - For biologic agents that have a prolonged half-life, the appropriate
interval since last treatment should be discussed with the PI prior to
first dose of vaccine.
- - Monoclonal antibody treatment: At least three half-lives must have elapsed
prior to first dose of vaccine.
Such participants should be discussed with the
PI prior.
- - Bone Marrow Transplant: Participant must be:
- ≥ 6 months since allogeneic bone marrow transplant prior to first dose of
vaccine.
- - ≥ 3 months since autologous bone marrow/stem cell prior to first dose of
vaccine.
- - Radiotherapy (in instances of lesions amenable to radiotherapy, such as bone
metastases or metastases causing nerve impingement): At least 4 weeks must have
elapsed prior to first dose of vaccine.
- - Investigational agents: At least 4 weeks must have elapsed prior to first dose
of vaccine.
- - Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm.
- - Platelets ≥ 100 K/cumm.
- - Hemoglobin level ≥ 8 g/dL.
- - 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.
- - Any adverse event patients may have experienced during prior therapy must have
resolved to ≤ CTCAE v5 grade 1.
- - Systemic corticosteroid therapy is permitted provided dosing is minimal based on
age, defined as 0.1mg/kg/day with a max of 4mg daily (dexamethasone or equivalent)
on the day of vaccine administration.
Participants using topical, ocular,
intra-articular, or intranasal/inhaled steroids may participate. Brief courses of
corticosteroids for prophylaxis (eg, contrast dye allergy) or study
treatment-related standard premedication are permitted.
- - Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and
to avoid high dose of corticosteroids.
- - 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.
Exclusion Criteria:
- - 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.
- - 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, symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements.
- - Ongoing or active infection requiring systemic therapy (e.g. active HBV or HCV
infection that requires treatment) or causing fever (temperature > 38.1˚C) or
subjects with unexplained fever (temperature > 38.1˚C) within 7 days prior to the
first vaccine dose.
- - History of immunodeficiency disorder or autoimmune condition requiring active
immunosuppressive therapy.
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.
- - Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL
or they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration.
Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended. Recommend exclusion of specific ART agents
based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates,
concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers
(efavirenz) should be contraindicated).
- - Administration of live vaccine within 30 days prior to first dose of vaccine.
Participants may receive the COVID-19 vaccine as long as it is not a live vaccine.
- - Presence of clinically significant increased intracranial pressure (e.g. impending
herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate
palliative treatment.
- - 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 measurement of the circumference of the thigh at the midpoint
between the hip and knee is < 35 cm.
- - Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
for eligible injection sites (left and right vastus laterals muscles) exceeds 50 mm.
- - Individuals in whom the ability to observe possible local reactions at the eligible
injection sites is, in the opinion of the investigator, unacceptably obscured due to
a physical condition (e.g. hypertrophic skin patches, keloids, or other conditions
which could interfere with the administration procedure or subsequent assessment of
local reactogenicity) or permanent body art.
- - Has a metal implant or implantable device within the area of the electroporation
injection or has any non-removable electronic stimulation device, such as cardiac
demand pacemaker, automatic implantable cardiac defibrillator, nerve stimulator, or
deep brain stimulator.
- - 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 first dose of vaccine.
