H3.3K27M-specific Peptide Vaccine and Poly ICLC in Treating Patients with Newly Diagnosed HLA-A2 Positive, H3.3K27M Positive Diffuse Intrinsic Pontine Glioma or Other Newly Diagnosed Gliomas including Spinal Cord Tumors
- Stratum A: Newly diagnosed children (3-21 years old) with DIPG who are positive for the H3.3K27M mutation (positive testing in Clinical Laboratory Improvement Act [CLIA] laboratory) that underwent standard radiation therapy
- Stratum B: Newly diagnosed children (3-21 years old) with diagnosis of glioma other than DIPG who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory) including spinal cord gliomas that underwent standard radiation therapy
- The patient must test positive for HLA-A2 (tested by a CLIA approved laboratory; only the HLA A*02:01 subtype is eligible)
- The patient must be either off systemic steroids or be on stable dose of dexamethasone (max 0.1 mg/kg/day; maximum 4mg/day) at time of enrollment
- Patients must not have received any prior chemotherapy, immunotherapy or bone marrow transplant for the treatment of their tumor; prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg/m^2 /dose continuously during radiation therapy for 42 days) or dexamethasone is allowed
- Patients must have undergone radiation therapy and surgery as part of their standard of care * Stratum A: Radiation therapy must have started within 4 weeks of diagnosis by imaging or surgery, whichever is later * Stratum B: For subjects undergoing surgery for more extensive resection, radiation therapy should be started within 4-6 weeks from surgery * H3.3K27 mutation must have been confirmed in the tumor tissue in a CLIA approved laboratory
- Karnofsky >= 50 for patients >= 16 years of age, and Lansky >= 50 for patients < 16 years of age; patients 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
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: * 3 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male) 1.4 (female) * >= 16 years: 1.7 (male) 1.4 (female)
- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L
- Serum albumin >= 2 g/dL
- Patients with seizure disorder may be enrolled if seizure disorder is well controlled
- Females of child-bearing potential and males must agree to use adequate contraception; adequate methods include: hormonal or barrier method of birth control; or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation
- Ability to understand a written informed consent document, and the willingness to sign it; assent will be obtained when appropriate based on the subjects age
- Investigational Drugs * Patients who are currently receiving another investigational drug are not eligible * Prior treatment with another investigational drug
- Anti-cancer Agents * Patients who are currently receiving other anti-cancer agents are not eligible * Prior treatment with other anti-cancer agents
- Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible; Note: patients that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair
- Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated)
District of Columbia
Salt Lake City
I. To assess the safety of repeated administration of the H3.3K27M-specific peptide vaccine (H3.3K27M epitope specific vaccine) in human leukocyte antigen (HLA)-A2+ children with H3.3K27M positive diffuse intrinsic pontine glioma (DIPGs).
II. To determine the overall survival at 12 months (OS12) in HLA-A2+ children with DIPG that are being treated with repeated administration of the H3.3K27M peptide.
I. Induction of the H3.3K27M epitope-specific cytotoxic T lymphocyte (CTL) response in post vaccine peripheral mononuclear cells (PBMC) in HLA-A2+ children with DIPG.
I. To assess the safety of repeated administration the H3.3K27M epitope specific vaccine in HLA-A2+ children with H3.3K27M positive gliomas other than DIPG including spinal cord gliomas.
II. Induction of the H3.3K27M epitope-specific CTL response in post vaccine peripheral mononuclear cells (PBMCs) in HLA-A2+ children with H3.3K27M positive gliomas other than DIPG.
III. Assessment of H3.3K27M infiltrates in subjects with evidence of progression that will undergo tissue collection as part of their standard of care.
IV. To archive tumor and normal deoxyribonucleic acid (DNA) from each patient at time of initial diagnosis along with serial blood draw following therapy for later studies to determine whether circulating tumor DNA (ctDNA) sequences in the patient’s blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance.
Beginning 2-8 weeks after completion of radiation therapy, patients receive H3.3K27M-specific peptide vaccine subcutaneously (SC) and poly ICLC intramuscularly (IM) on day 1. Treatment repeats every 3 weeks for up to 8 courses (week 21) in the absence of disease progression or unacceptable toxicity. Beginning week 30, patients with stable to improved disease may receive additional vaccines every 6 weeks thereafter for up to 2 years (96 weeks) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 24 months.
Trial Phase Phase I
Trial Type Treatment
UCSF Medical Center-Mount Zion
- Primary ID 150819
- Secondary IDs NCI-2017-01830, 16-20574, PNOC 007
- Clinicaltrials.gov ID NCT02960230