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

NCT02772094 | Unknown Phase 2

• 1 other identifier: DMR94-IRB-043-1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma Multiforme; Glioblastoma

Keywords

glioblastoma multiforme; glioblastoma; newly diagnosed glioblastoma; immunotherapy; dendritic cells; grade IV astrocytoma; oncology; neurology; glioma; brain tumor; ADCTA-G

Outcome Measures

Primary Outcomes (2)

• Overall survival with measures of medium survival period (in days) and annual survival rates (in %)

  The primary end-point is overall survival (OS), days measured from post-recruitment surgery date (tumor resection or biopsy) to date of death due to GBM or other causes, and if alive, to date of weekly phone calls and health care visit every 3 months, up to 6 years. Survival days of patients are depicted on Kaplan-Meier plots to show the medium survival period (days when 50% patients remained alive) and annual rates (% living patients per total) every year up to 5 years, and by log rank test to find statistical probability p value. Study groups of ADCTA-G immunotherapy plus conventional multimodal regimen will be compared to reference groups treated with conventional multimodal regimen (no ADCTA or other immunotherapy).

  Post-recruitment surgery to death due to GBM or any other causes; close follow-up at leas by biweekly health care or emergency visits for 24 months, then weekly phone calls and scheduled visits at least every 3 months, up to 6 years after surgery

• Adverse effects, acute and chronic, assessed according to NCI CTCAE Version 3

  Acute or delayed/chronic adverse effects, graded according to NCI CTCAE Version 3.0, e.g. temozolomide combined chemo-radiotherapy(CCRT)-/GBM-caused lymphopenia, measured by lymphocytes/microL blood, and by % of patients with lymphopenia of grade 1, 2, 3, or 4 severity.

  Post-recruitment surgery to death, due to ADCTA-G, GBM disease or temozolomide chemotherapy; if alive, bi-weekly follow up for 24 months after surgery and then at least one visit in 3 months, up to 72 months

Secondary Outcomes (1)

• Disease progression-free period

  From recruitment surgery to death, or if alive, biweekly for 24 months, and then weekly phone calls and at least once in 3 months, up to 72 months

Study Arms (1)

Single arm, open-label

EXPERIMENTAL

Experimental: ADCTA-G total 10 doses, each dose (30+/-5 millions autologous dendritic cells plus 6+/-0.5 millions 100Gy-irradiated short-term cultured autologous GBM tumor cells) divided in 2 halves for subcutaneous injection into both axillar areas, in a course of 6 months (sequential series of weekly injections 4 times, bi-weekly injections twice; then monthly injections 4 times. Experimental: ADCTA-G total 10 doses, each dose (similar fore-mentioned numbers of 5:1 ratio of autologous dendritic cells and irradiated short-term cultured autologous GBM tumor cells) divided into 2 injections administered subcutaneously in both axillar areas, in a course of 8 months (sequential series of bi-weekly injections 4 times, then monthly injections 6 times).

Biological: Single arm, open-label

Interventions

Single arm, open-label BIOLOGICAL

Biological: ADCTA-G. Biological: autologous DC loaded with irradiated autologous tumor cells. Biological: dendritic cell "vaccine". Drug: 180mg/m2•per day temozolomide prior and concomitant with radiotherapy. Radiotherapy: Local ionizing radiation 200 centigray(cGy)/day, 5 successive days per week for 6 weeks, total dose of 6000 cGy. Drug: Adjuvant chemotherapy-temozolomide (TMZ) monthly cycle, 200mg/m2•per day continued for 5 days in the beginning of every month, 6 cycles of TMZ.

Also known as: ADCTA-G

Single arm, open-label

Eligibility Criteria

• Age: 13 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically proved WHO grade-4 malignant glioma
• Age: 13 years (physically mature) to 70 years
• Karnofsky performance score before surgery: ≧70 \[Karnofsky 1951\] .
• 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
• Adequate renal function (BUN ≤25 mg/ml; creatinine≤1.8 mg/dl，creatinine clearance \>50 ml/min prior to starting therapy
• Hemoblobin≧8 g/dl，platelet ≧100,000/μl，WBC\>2,000/μl; absolute neutrophil count \>1,000/μl
• Prothrombin time and partial thromboplastin time≦1.5x the normal upper limit

You may not qualify if:

• Pregnant or breast feeding
• With radioactive implant
• Acute infection, fever
• Active collagen diseases
• Acute cardiovascular diseases
• Acute viral hepatitis
• Syphilis
• Human immunodeficiency virus (HIV) infection
• Carrier of other transmissible infection
• Immune deficiency due to chronic disease

Sponsors & Collaborators

• China Medical University Hospital: lead
• Den-Mei Brain Tumor Education Foundation, Taichung, Taiwan: collaborator
• Ministry of Health and Welfare, Taiwan: collaborator

Study Sites (1)

China Medical University Hospital

Taichung, 404, Taiwan

Location

Related Publications (1)

• Chang 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 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Neoplasms; Glioma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Wen-Kuang Yang, M.D. PhD.

  China Medical University Hospital, Taichung Taiwan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Chair Professor

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: May 13, 2016
• Study Start: May 1, 2005
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2016
• Last Updated: May 13, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share

Locations

TW (1)