Inclusion Criteria:

• Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
• ≤ 30 years at the time of initial diagnosis with high-risk disease
• * Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
• Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:
• Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
• Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
• Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
• Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
• Patients must have a body surface area (BSA) ≥ 0.25 m^2
• No prior anti-cancer therapy except as outlined below:
• Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
• Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
• Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
• Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• A serum creatinine based on age/sex as follows:
• 1 month to < 6 months: Male 0.4 mg/dL and female 0.4mg/dL
• 6 months to < 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
• 1 to < 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
• 2 to < 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
• 6 to < 10 years: Male 1 mg/dL and female 1 mg/dL
• 10 to < 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
• 13 to < 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
• ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL
• The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
• or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 or
• or a GFR ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
• Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase [ALT]) ≤ 10 x ULN*
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• * Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
• Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:No known contraindication to PBSC collection. Examples of contraindications might be aweight or size less than the collecting institution finds feasible, or a physicalcondition that would limit the ability of the child to undergo apheresis catheterplacement (if necessary) and/or the apheresis procedure

Exclusion Criteria:

• Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
• Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
• Patients with known bone marrow failure syndromes
• Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
• Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, food and drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Inclusion Criteria:

• PRE-ENROLLMENT: Patients must be ≥ 4 years and ≤ 21 years of age at the time of enrollment
• PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis
• Please note: Patients with a pending result of CSF cytology tests are eligible for NCI-2014-02057 (APEC14B1-Central Nervous System [CNS]) and CNS/Medulloblastoma Pre Enrollment Eligibility Screening
• PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening and consent for the Molecular Characterization Initiative (MCI)
• PRE-ENROLLMENT: The required specimens are projected to be submitted under APEC14B1-CNS as soon as possible, preferably within 5 days of definitive surgery
• PRE-ENROLLMENT: All patients must have rapid central pathology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1 in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031.
• Note: Patients with a pending result of CSF cytology tests are eligible for the rapid central pathology screening review. Confirmation of CSF negativity is needed for enrollment on the ACNS2031 protocol
• PRE-ENROLLMENT: All patients must have rapid central molecular screening review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1, in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031
• PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central imaging screening review under APEC14B1 prior to study enrollment on ACNS2031 step 1
• Note: Patients must not have metastatic disease on cranial or spinal MRI. Patients with > 1.5 cm^2 residual tumor after initial surgical resection may undergo a second surgical resection prior to subsequent therapy to render them eligible for this study. The day of the second resection to remove residual tumor will be regarded as the day of definitive surgery (Day 0) and must be within a month (31 days) of the initial resection
• PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central audiology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1
• Patients must be >= 4 years and =< 21 years of age at the time of enrollment
• Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative
• Average-risk cohort
• Clinico-pathologic criteria:
• M0 disease
• No diffuse anaplastic histology AND
• Molecular criteria:
• SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss
• Group 3, MYC normal, no isochromosome 17q
• Group 4, no chromosome 11 loss
• Low-risk features cohort
• Clinico-pathologic criteria:
• M0 disease
• No diffuse anaplastic histology AND
• Molecular criteria:
• Group 4, chromosome 11 loss
• Patients must have negative lumbar CSF cytology
• Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
• Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have =< 1.5 cm^2 cross-sectional area of residual tumor. Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed
• Patients must weigh > 10 kg
• Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (day 0)
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell count [RBC] transfusions) (within 7 days prior to enrollment)
• A serum creatinine (within 7 days prior to enrollment) based on age/sex as follows:
• 4 to < 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female)
• 6 to < 10 years (age); 1 mg/dL (male) 1 mg/dL (female)
• 10 to < 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female)
• 13 to < 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female)
• >= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urine Creatinine clearance >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment
• Auditory function defined as:
• Patients must have normal hearing (defined as International Society of Pediatric Oncology [SIOP] grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
• Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
• Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)
• Pregnancy and Breastfeeding:
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Inclusion Criteria:

• Patients must be ≥ 3 years and < 30 years at the time of study enrollment
• Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required
• Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) AND hCGbeta ≤ 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. No histologic confirmation required
• Patients with hCGbeta 51-100 mIU/mL in serum and/or CSF and institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. Histologic confirmation of germinoma IS required
• Patients with germinoma of the basal ganglia and or/thalamic primary sites are eligible
• Patients with metastatic germinoma including non-contiguous disease or distant disease in the brain, ventricles, or spine are eligible
• Patients with germinoma admixed with mature teratoma are eligible
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
• Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1-CNS
• Imaging studies must be obtained within 31 days prior to study enrollment and start of protocol therapy. (Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI that must be obtained within 31 days prior to enrollment.)
• Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post-operative brain MRI with and without gadolinium. The post-operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment
• Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later
• Patients must have eligibility confirmed by Rapid Central Tumor Marker Review performed on APEC14B1-CNS
• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery. Of note, lumbar CSF should not be performed prior to obtaining spine MRI, as this can make interpretation of the spine MRI less clear
• Patients must have CSF tumor markers obtained prior to study enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first. Ideally serum and CSF tumor markers should be collected at the same time and processed without delay
• For patients with solid tumors: Peripheral absolute neutrophil count (ANC) >= 1000/uL (Must be performed within 7 days prior to enrollment unless otherwise indicated)
• For patients with solid tumors: Platelet count >= 100,000/uL (transfusion independent) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
• For patients with solid tumors: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
• For pediatric patients (age 3-17 years): A serum creatinine based on age/gender as follows (Must be performed within 7 days prior to enrollment unless otherwise indicated):
• Age: 3 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female)
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male); 1 (female)
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
• Age: ≥ 17 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) OR a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 OR a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
• Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
• For adult patients (age 18 years or older) (Must be performed within 7 days prior to enrollment unless otherwise indicated):
• Creatinine clearance ≥ 70 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (Must be performed within 7 days prior to enrollment unless otherwise indicated)
• Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) ≤ 135 U/L (Must be performed within 7 days prior to enrollment unless otherwise indicated)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• CNS toxicity =< grade 2
• Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load are eligible for this study

Exclusion Criteria:

• Patients with any of the following malignant pathological elements are not eligible:
• Endodermal sinus (yolk sac)
• Embryonal carcinoma, choriocarcinoma
• Malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some germinoma)
• Patients with only mature teratoma upon tumor sampling at diagnosis and negative tumor markers are not eligible
• Patients who have received any prior tumor-directed therapy for their diagnosis of germinoma other than surgical intervention and corticosteroids are not eligible
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:
• Non-small cell lung cancer
• Melanoma
• Breast cancer
• Renal cell carcinoma
• Gastrointestinal cancer
• If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, positron emission tomography [PET]/CT, etc.) is required
• Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration
• At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm
• All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension
• Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS/FSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator
• Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5
• No more than 2 lesions planned for resection if clinically indicated
• No known leptomeningeal disease (LMD)
• Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
• Age ≥ 18 years
• Karnofsky performance status (KPS) ≥ 60
• Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation [PCI])
• New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
• No active infection currently requiring intravenous (IV) antibiotic management
• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy

Inclusion Criteria:

• Histologically-proven glioblastoma (World Health Organization [WHO] 2021 criteria)
• Progressive or recurrent disease per Response Assessment in Neuro-Oncology (RANO) criteria
• No IDH mutation (IDH1 R132H negative by immunohistochemistry [IHC] or sequencing)
• Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
• No prior therapies except radiation, surgery, temozolomide, Tumor Treating Fields (TTFields), and/or Gliadel wafers (placed during the first surgery at diagnosis of glioblastoma multiforme [GBM]). Prior radiation therapy, TTFields, or placement of Gliadel wafers must be completed at least 2 weeks prior to registration. Prior temozolomide must be completed at least 3 weeks prior to registration
• No prior use of nivolumab or other anti-PD1 agents
• Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration
• Age: ≥ 18 years
• Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others)
• Absolute lymphocyte count (ALC): ≥ 1000/mm^3
• Absolute neutrophil count (ANC): ≥ 1500/mm^3
• Platelet count: ≥ 100,000/mm^3
• Hemoglobin: ≥ 9.0 g/dL
• Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT): ≤ 1.5 x upper limit of normal (ULN)
• Total bilirubin: < 2.0 x ULN (Except for patients with Gilbert's syndrome, who must have direct bilirubin < 2.0 x ULN)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT): < 3.0 x ULN
• Calculated (calc.) creatinine clearance (CrCl): ≥ 50 mL/min
• Calculated by Cockcroft-Gault equation
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done within 14 days prior to registration is required
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• No active brain metastases or leptomeningeal disease
• HIV: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
• Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• No known medical condition causing an inability to swallow oral formulations of agents
• No current symptomatic pulmonary disease
• No autoimmune disorders that require systemic treatment (except hyperthyroidism or diabetes mellitus)

Inclusion Criteria:

1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Age 18 years or older 4. Presumed diagnosis of glioblastoma IDH-wt (as per the 2021 WHO Classification of CNS Tumors) deemed to be potentially resectable and deemed to be a good candidate for post-operative standard of care temozolomide and radiation therapy. 1. Surgical objective is for gross total resection (GTR)ear-total resection (NTR) de-fined as ≥ 95% of contrast enhancing (CE) tumor removed plus ≤ 1 cm3 residual CE tumor. Patients with subtotal resection will still be eligible if at least 70% of the CE tumor is resected. 2. Eligibility will be confirmed after surgery when diagnosis of glioblastoma IDH-wt confirmed prior to randomization. Randomization can occur with only IDH1 immunohistochemistry and when additional molecular testing is available, if glioblastoma IDH-wt is not confirmed, the participant will be deemed a screen failure and replaced. 3. Patients with prior biopsy or subtotal resection are eligible if no other anti-cancer treatment received for glioblastoma and additional resection indicated. 5. Ability to receive filgrastim (e.g., Neupogen), leukapheresis and 3 bi-weekly injections of DOC1021 near deep cervical lymph nodes + weekly pIFN x 6 weeks. 6. Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as determined appropriate for the patient by the investigator) during study treatment. 7. Adequate kidney, liver, bone marrow function, and immune function, as follows: 1. Hemoglobin ≥ 8.0 gm/dL 2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 3. Platelet count ≥ 75,000/mm3 4. Calculated creatinine clearance (CrCl) > 30 mL/min using Cockcroft and Gault for-mula: i. For males = (140 - age[years]) x (body weight [kg]) / (72 x serum creatinine [mg/dL]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 2 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN 8. Karnofsky Performance Score ≥ 70

Exclusion Criteria:

1. Infratentorial, recurrent, leptomeningeal or extracranial disease. 2. Patients who are pregnant or breastfeeding. 3. Known active HIV or hepatitis infection. Patients with HIV that is well-controlled and have undetectable viral titers remain eligible. Patients with history of HCV adequately treated such that RNA viral load is negative also remain eligible. 4. Any severe or uncontrolled medical condition or other condition that could affect participation in this study as determined by the investigator, including but not limited to: uncontrolled or severe cardiac disease, systemic autoimmune disorders requiring immunosuppression in the past 2 years*, autoimmune hyper/hypothyroidism, untreated viral hepatitis, autoimmune hepatitis. *autoimmune disorders include but are not limited to rheumatoid arthritis, psoriasis and inflammatory bowel disease and immunosuppressive medications include DMARDs like methotrexate, TNF inhibitors, IL-6 receptor blockers, CD80/86 inhibitors, anti-CD20 and JAK inhibitors 5. Treatment with another investigational drug or other experimental intervention within the last 30 days.