ADCTA for Adjuvant Immunotherapy in Standard Treatment of Recurrent Glioblastoma Multiforme (GBM)

Inclusion Criteria:

1. Specimen collection screening

   * Karnofsky performance status (KPS) ≥ 60 at assessment prior to surgery
   * ≥ 18 and ≤ 70 years of age
   * Subject has been diagnosed with GBM and has undergone resection surgery followed by standard brain RT + concurrent temozolomide and adjuvant temozolomide, and progression occurred. The foregoing progression is defined as when patients with primary GBM experience an image or clinical deterioration after receiving standard of care.
   * Contrast-enhanced MRI suspects recurrent GBM
   * Supratentorial tumor
   * Must voluntarily sign and date informed consent form for specimen acquisition and future use, for study screening, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures
2. Study screening

   * Karnofsky performance status (KPS) ≥ 60 at randomization
   * Submission of fresh tumor
   * Post-operation contrast-enhanced MRI scan must be done after surgical resection, with the intent for cyto-reduction ≥ 80% of the contrast-enhancing tumor mass
   * Histologically confirmed WHO grade IV glioma by pathology tissue screening
   * Subjects receiving bevacizumab as standard of care for given indication
   * Subject has adequate bone marrow, renal, and hepatic function prior to randomization as follow:

     1. White blood cell (WBC) count ≥ 2,000/mm\^3;
     2. Absolute neutrophil count (ANC) ≥ 1,000/mm\^3;
     3. Platelets ≥ 100,000/mm\^3;
     4. Hemoglobin (Hgb) ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable.);
     5. Blood Urea Nitrogen (BUN) \< 30 mg/dL;
     6. Creatinine \< 2 mg/dL;
     7. Renal function: calculated creatinine clearance ≥ 30 mL/min;
     8. Hepatic function: Total bilirubin ≤ 3 times upper limit of normal (ULN), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 times ULN;
     9. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6 times ULN unless therapeutically warranted.
   * Subjects with recurrent GBM (Grade IV) are eligible for this protocol. An independent neuropathologist will review this diagnosis during the enrollment process
   * Must voluntarily sign and date informed consent form, for study participation, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures

Exclusion Criteria:

1. Specimen collection screening

   * Multifocal GBM
   * Prior invasive malignancy (except for non-melanomatous skin cancer; carcinoma in situ of breast, oral cavity or cervix) unless disease free for ≥ 2 years
   * Subject has used bevacizumab or immune checkpoint blockade to treat GBM
   * Lactating or pregnant female
   * Positive viral serology for HIV or syphilis at time of screening
2. Study screening

   * Subjects having a biopsy only at surgery or tumor cell insufficiency at preparation
   * Inability to undergo contrast-enhanced MRI scans
   * Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia)
   * Inability to stop or decrease the use of corticosteroid doses to 4 mg/day prior to randomization
   * Tumor progression documented according to modified RANO criteria prior to randomization (approximately 5 weeks after surgery)
   * Severe, active comorbidity, defined as follow:

     1. Subject with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness;
     2. Subjects with acute hepatitis C or B infection;
     3. Severe hepatic impairment (Child-Pugh category C or higher);
     4. Electrocardiogram (ECG) with evidence of acute cardiac ischemia prior to randomization;
     5. Transmural myocardial infarction or ischemia prior to enrollment;
     6. Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administration or completion of protocol therapy
   * Subject used Gliadel wafer implant in surgery during screening process