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

Autologous Dendritic Cell / Tumor Antigen (ADCTA-SSI-G1) for Adjuvant Immunotherapy in Standard Treatment of Recurrent Glioblastoma Multiforme (GBM): A Multi-center, Open-label, Randomized Phase III Clinical Trial

To confirm the result of previous Phase I/II and phase II clinical trials, this trial is to test the efficacy and safety of ADCTA immunotherapy plus the standard therapy in comparison with standard therapy alone in patients with recurrent 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