Testing the Safety, Tolerability and Immunological Effects of SurVaxM in Children and Young Adults with Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Inclusion Criteria

• SCREENING: Progressive or Recurrent Patients: Patients with a histologically confirmed diagnosis of a primary central nervous system (CNS) tumor that is progressive or recurrent defined as radiographic progression in any known residual tumor, or the appearance of one or more new lesions, leptomeningeal disease, or new cerebrospinal fluid (CSF) positivity for malignant cells, after after most recent treatment modality. At the time of diagnosis or recurrence, all tumors must have histologic verification of one of the following: * Medulloblastoma * Glioblastoma multiforme (GBM) * Anaplastic astrocytoma * High-grade astrocytoma, not otherwise specified (NOS) * Anaplastic oligodendroglioma * Anaplastic ependymoma (World Health Organization [WHO] grade III) * Ependymoma (WHO grade II)
• SCREENING: Diffuse Intrinsic Pontine Gliomas (DIPG) Patients: Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of 2/3 or more of the pons, are eligible without histologic confirmation and will proceed directly to enrollment without screening
• SCREENING: Patients must provide tumor tissue (3 unstained slides or paraffin block) to determine their survivin expression status. Demonstration of survivin expression of at least 1% on tumor tissue by immunohistochemistry is required and must be performed in the central laboratory at Roswell Park Comprehensive Cancer Center (RPCCC) to confirm eligibility
• SCREENING: Patients must be >= 1 year of age and =< 21 years of age at the time of screening
• SCREENING: Participant is willing to sign a screening consent. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines
• SCREENING: Patients screened for this trial should be expected to meet the criteria for treatment below
• Histologic diagnosis (at initial diagnosis or recurrence) of one of the following: * Medulloblastoma * Glioblastoma multiforme (GBM) * Anaplastic astrocytoma * High-grade astrocytoma, NOS * Anaplastic oligodendroglioma * Anaplastic ependymoma (WHO Grade III) * Ependymoma (WHO Grade II)
• Patients with diffuse intrinsic pontine gliomas (DIPGs) will be eligible 14 to 56 days post-completion of radiation therapy if they do not have any evidence of progression * Patients with a typical DIPG on MR imaging, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation ** Note: Patients with typical DIPG who undergo a biopsy are eligible provided the tumor is a diffuse glioma WHO grade II-IV with OR without H3 K27M mutation * Patients with pontine lesions that do not meet these MR imaging criteria will be eligible if there is histologic confirmation of diffuse glioma WHO grade II-IV with H3 K27M mutation
• For patients with relapsed or progressive medulloblastoma, HGG, or ependymoma, demonstration of survivin expression as assessed after screening consent/assent of at least 1% on tumor tissue by immunohistochemistry (ICH) is required and must have been performed in the central laboratory at Roswell Park Comprehensive Cancer Center (RPCCC) to confirm eligibility. For patients with DIPG, diagnostic biopsy for histologic confirmation is not required, and tumor expression of survivin is therefore not required for eligibility for these patients
• Patients must have evaluable disease within the central nervous system to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows: * Measurable disease: bi-dimensionally measurable disease; at least one lesion that can be accurately measured in at least two dimensions * Non-measurable disease: ** A lesion that does not meet the criteria for measurable disease as defined above; or ** Diffuse leptomeningeal disease, or ** No tumor visible on imaging but presence of malignant cells on cytologic examination of cerebrospinal fluid (CSF)
• Stratum 1 (progressive or recurrent) patients must be >= 10 years of age and =< 21 years of age at the time of study screening
• Stratum 2 (progressive or recurrent) patients must be >= 1 year of age and < 10 years of age at the time of study screening
• Stratum 3 (newly diagnosed DIPG) patients must be >= 1 year of age and =< 21 years of age at the time of study enrollment
• Patients with recurrent or progressive disease must have received prior chemotherapy and/or radiotherapy
• Patients with newly diagnosed DIPG must have completed radiation therapy
• Patients must have recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria; excludes alopecia) prior to entering this study
• Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea. Patients must have received their last dose of non-myelosuppressive chemotherapy at least 7 days prior to enrollment
• Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment. * For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibody treatment and agents with known prolonged half-lives: Patient must have received their last dose of the agent >= 28 days prior to study enrollment.
• Patients with recurrent or progressive CNS tumor must have had their last fraction of: * Craniospinal irradiation, whole brain radiation, total body irradiation or radiation to spine >= 6 weeks (42 days) prior to enrollment. * Focal irradiation >= 14 days prior to enrollment
• Patients with DIPG are eligible after completion of initial radiotherapy (with or without concurrent treatment) and in the absence of progressive disease on post-radiation imaging. Patients must have completed radiation therapy at least 14 days prior to enrollment but no longer than 56 days and cannot have received any other tumor-directed treatment except the following: * Patient may have received temozolomide or other non-investigational agents during irradiation at the treating physician’s discretion. If the patient has received such agents concurrently with radiation, then patient must have recovered from the acute treatment related toxicities (defined as < grade 1) prior to enrollment
• Patient must be: * >= 24 weeks (168 days) since allogeneic stem cell transplant prior to enrollment with no evidence of active graft versus (vs.) host disease. * >= 12 weeks (84 days) since autologous stem cell transplant prior to enrollment. * > 42 days since completion of any other type of adoptive cellular therapy prior to enrollment
• Patients must be at least 14 days from recent cranial surgery (ventriculoperitoneal [VP] shunt, endoscopic third ventriculostomy [ETV], tumor resection) at the time of enrollment
• Patients with neurological deficits should have deficits that are stable for a minimum 7 days of prior to enrollment. A baseline neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study
• Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within 14 days prior to enrollment must be >= 60. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Absolute neutrophil count >= 0.75 x 10^9 cells/L
• Platelets >= 100 x 10^9 cells/L (unsupported, defined as no platelet transfusion within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may receive transfusions)
• Prothrombin time (PT)/institutional normalized ratio (INR), partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x institutional upper limit of normal (ULN)
• Albumin >= 2 g/dL
• Blood creatinine based on age/gender. Patients that do not meet the criteria but have a 24 hour creatinine clearance or glomerular filtration rate (GFR) (radioisotope or iothalamate) >= 70 mL/min/1.73 m^2 are eligible. * Age 1 to < 2 years, maximum blood creatinine (mg/dL) male 0.6, female 0.6 * Age 2 to < 6 years, maximum blood creatinine (mg/dL) male 0.8, female 0.8 * Age 6 to < 10 years, maximum blood creatinine (mg/dL) male 1, female 1 * Age 10 to < 13 years, maximum blood creatinine (mg/dL) male 1.2, female 1.2 * Age 13 to < 16 years, maximum blood creatinine (mg/dL) male 1.5, female 1.4 * Age >= 16 years, maximum blood creatinine (mg/dL) male 1.7, female 1.4
• Patients who are known to be Human immunodeficiency virus (HIV)-infected must be on effective anti-retroviral therapy with undetectable viral load for 24 weeks (168 days) prior to study enrollment
• For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with known HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 7 days prior to enrollment. A maximum dose of 0.1 mg/kg/day (and maximum total daily dose 4 mg) of dexamethasone (or equivalent) is permitted at study entry. Effort should be made to reduce to lowest tolerated steroid dose. Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
• Patients must be off all colony-forming growth factor(s) for at least 14 days prior to enrollment (e.g., filgrastim, sargramostim, or erythropoietin). Fourteen (14) days must have elapsed if the patient received a long-acting formulation
• Pregnant women or nursing mothers are excluded from this study because SurVaxM is an agent with the potential for teratogenic effects. Female patients of childbearing potential must have a negative serum or urine pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
• The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

• Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SurVaxM
• Patients with spinal cord primary tumors
• Patients with relapsed or progressive DIPG
• Patients with metastatic DIPG are not eligible. MRI of spine must be performed if disseminated disease is suspected by the treating physician
• Patients with midline high grade gliomas including those with H3 K27M-altered diffuse midline glioma (DMG) centered outside of the pons
• Patients with grade II myxopapillary ependymoma
• Patients with WHO grade I or II gliomas are not eligible unless tumor is defined as a DIPG
• Patients with bone-only metastatic lesions that do not have otherwise evaluable CNS disease
• Patients with bulky tumor on imaging are ineligible. Bulky tumor is defined as any of the following: * Tumor with evidence of clinically significant tonsillar herniation * Tumor with evidence of clinically significant uncal herniation causing midbrain compression or midline shift greater than 5 mm * Tumor with a diameter > 4 cm in one dimension on T2/FLAIR * Tumor that in the opinion of the site investigator, shows significantly rapid progression of mass effect in either the brain or spinal cord such that the priming phase of vaccination (i.e., 6 weeks) cannot be completed before clinical deterioration is likely to occur. * Treating physicians should contact the study chair to request a rapid central imaging review to confirm fulfilment of these eligibility criteria, if they have concerns. If clinically appropriate, surgical debulking of large tumors should be considered before study entry
• Active, uncontrolled infection requiring treatment (including HIV infection)
• Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, with the exception of: * Patients with vitiligo or resolved asthma/atopy * Patients with hypothyroidism stable on hormone replacement or Sjogren’s syndrome
• History of or ongoing pneumonitis or significant interstitial lung disease
• Patients with any clinically significant unrelated systemic illness (significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial
• Any medical condition that, in the opinion of the principal investigator, would compromise the patient’s ability to participate in the study
• Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
• Patients who are receiving any cannabidiol (CBD) or medical marijuana treatment are ineligible
• Patients who have received the last vaccination of a live vaccine =< 30 days prior to enrollment are ineligible. * Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and must meet timeline for live vaccine
• Patients who have received an inactivated virus, peptide, or messenger ribonucleic acid (mRNA) vaccine within 14 days of the start of protocol therapy are ineligible
• Patients may not be on immunosuppressive therapy, including corticosteroids at time of enrollment. However, patients who require intermittent use of bronchodilators, local steroid injections, or topical steroids will not be excluded from the study
• Patients may not be receiving allergy desensitization injections or interleukins at the time of enrollment
• Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity of therapy or to adhere to drug administration plan, other study procedures, and study restrictions
• Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), granulocyte colony-macrophage stimulating factor (sargramostim) or MRI contrast agent
• Patients with a known coagulopathy or bleeding diathesis or requires the use of systemic, anticoagulant medication are not eligible