Dendritic Cell-Based Tumor Vaccine Adjuvant Immunotherapy of Human Glioblastoma Multiforme (WHO Grade IV Gliomas)

Purposes: The purpose of this phase-II clinical trial is to determine whether or not ADCTA-G, a biologic "vaccine" preparation of patient's own dendritic cell (DC) for glioblastoma multiforme (GBM) treatment, is safe and effective in extending the GBM patient's life. The current conventional multi-modal regimen that may include surgery for tumor resection or biopsy, temozolomide (TMZ) combined chemo-radiotherapy (CCRT) and TMZ adjuvant chemotherapy almost always leaves residual GBM cells to cause fatal recurrence, leading to medium survival period of 8 -15 months and over-all survival rates of about 30% in 2 years and \<3% in 5 years after diagnosis/surgery. Thus, in neurosurgical oncology practice, GBM patients in the first 2-year period during and after receiving multi-modal therapy are watched closely for possible GBM tumor recurrence and mortal disease relapse and immediately given palliative treatments and health care, until death. In this phase-II trial, GBM patient participants who receive ADCTA-G "vaccine" adjuvant immunotherapy (added to the conventional multi-modal regimen) will be similarly watched closely by treatments and health care visits at least biweekly from the date of surgery/diagnosis to 24 months, and if alive followed by weekly phone calls and scheduled health care visits at least once every 3 months, up to 72 months after surgery. In the trial protocol, ADCT-G in 10 doses is administered after surgery, over a period of 6 or 8 months, as an adjuvant immunotherapy of the conventional multimodal regimen. Individual ADCTA-G "vaccine" lot of every participant GBM patient is manufactured from patient's own monocyte-derived dendritic cells and the patient's own tumor cell antigens, both of which are prepared by a distinct method of procedures performed within air particle-free barrier good laboratory practice (GLP) facility. Previous phase I/II clinical trial of ADCTA-G "vaccine" immunotherapy administered as an adjuvant to the conventional multimodal regimen, has obtained promising safety and efficacy results for GBM patients in a clinical center. This phase-II clinical trial in China Medical University Hospital-Taichung will employ essentially the same clinical protocols and the same distinct "vaccine" manufacturing method of standard operational procedures (SOP), that is, the conventional multimodal regimen plus adjuvant immunotherapy using personal ADCTA-G "vaccine" lot for every GBM patient participants.

Sex

All

Minimum age

13 Years

Maximum age

70 Years

Inclusion Criteria:

1. Histopathologically proved WHO grade-4 malignant glioma
2. Age: 13 years (physically mature) to 70 years
3. Karnofsky performance score before surgery: ≧70 \[Karnofsky 1951\] .
4. Adequate liver functions, including serum alanine aminotransferase (ALT or SGPT), serum aspartate aminotransferase (AST or SGOT), and alkaline phosphatase at ≤3.0 times upper limits of normal levels (ULN), total bilirubin ≤1.5mg/dl), total serum bilirubin \<3 mg/dl
5. Adequate renal function (BUN ≤25 mg/ml; creatinine≤1.8 mg/dl，creatinine clearance \>50 ml/min prior to starting therapy
6. Hemoblobin≧8 g/dl，platelet ≧100,000/μl，WBC\>2,000/μl; absolute neutrophil count \>1,000/μl
7. Prothrombin time and partial thromboplastin time≦1.5x the normal upper limit

Exclusion Criteria:

1. Pregnant or breast feeding
2. With radioactive implant
3. Acute infection, fever
4. Active collagen diseases
5. Acute cardiovascular diseases
6. Acute viral hepatitis
7. Syphilis
8. Human immunodeficiency virus (HIV) infection
9. Carrier of other transmissible infection
10. Immune deficiency due to chronic disease

• BACKGROUNDChang CN, Huang YC, Yang DM, Kikuta K, Wei KJ, Kubota T, Yang WK. A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci. 2011 Aug;18(8):1048-54. doi: 10.1016/j.jocn.2010.11.034. Epub 2011 Jun 28. PMID 21715171