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 followedby standard brain RT + concurrent temozolomide and adjuvant temozolomide, andprogression occurred. The foregoing progression is defined as when patients withprimary GBM experience an image or clinical deterioration after receivingstandard of care.

• Contrast-enhanced MRI suspects recurrent GBM

• Supratentorial tumor

• Must voluntarily sign and date informed consent form for specimen acquisition andfuture use, for study screening, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of anystudy-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 torandomization 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 otherintervention 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) ≤ 2times ULN;

9. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6times ULN unless therapeutically warranted.

• Subjects with recurrent GBM (Grade IV) are eligible for this protocol. Anindependent neuropathologist will review this diagnosis during the enrollmentprocess

• 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 insitu 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 atpreparation

• Inability to undergo contrast-enhanced MRI scans

• Subjects receiving investigational study drug for any indication orimmunological-based treatment for any reason (Filgrastim may be used forprevention of severe neutropenia)

• Inability to stop or decrease the use of corticosteroid doses to 4 mg/day priorto randomization

• Tumor progression documented according to modified RANO criteria prior torandomization (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 torandomization;

5. Transmural myocardial infarction or ischemia prior to enrollment;

6. Any other major medical illnesses or psychiatric impairments that in theInvestigator's opinion will prevent administration or completion of protocoltherapy

• Subject used Gliadel wafer implant in surgery during screening process