Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme

MRI & pheresis post vaccine

Time frame: Day 42

Population: All participants who received all 3 vaccine administrations were used in this data analysis.

Peripheral blood obtained before starting radiation/ temozolomide (TMZ), and at first and second leukapheresis will be used to do lymphocyte phenotyping. We will determine percentages of CD3+/CD8+/CD45RO+ (memory T-cells), CD3+/CD8+/CD28- (CD8 suppressor T cell phenotype), and CD4+/CD25+ cells at those 3 time points. An anti-human Foxp3 antibody will be used to determine if the CD4+/CD25+ cells are T regulatory cells (TREG) and how the compartmental shift correlates with immunoresponse by other immune parameters as well as to efficacy.

Time frame: Before starting radiation/Temozolomide and at Day 7 and Day 42.

Pre- and post-vaccine immune assay results (Tumor-specific T-cells ) are summarized on a continuous scale as mean.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)

Population: proportion of cells responding to GBM; GBM = glioblastoma multiforme

Pre- and post-vaccine immune assay results (Tumor-specific T-cells ) are summarized on a continuous scale as median.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination).

Population: proportion of cells responding to GBM; GBM = glioblastoma multiforme

Pathologic specimen obtained from patients who require of another surgical resection after vaccination will be examined to determine the characteristics of infiltrating tumor cells. Paraffin sections of tumor specimen will be stained by immunohistochemistry with antibodies to identify the components of the inflammatory response. This specimen will be compared to the one obtained at the time of initial surgery and changes in inflammation and inflammatory cellular components will be noted.

Time frame: Approximately 42 months

Population: Number of patients with pre- and post-tumor tissue procured, to undertake a meaningful analysis of the tumor immunohistochemistry slides inflammatory cells was insufficient. No data was collected.

Adverse events attributed to vaccination. Collected and attributed adverse events at each study visit; monitored participants for adverse events for two hours following vaccination procedure.

Time frame: Until death or approximately 24 months after diagnosis

Population: Participants were monitored for adverse events at each visit and observed for 2 hours after intranodal injections. Toxicities were graded using the Common Terminology Criteria for Adverse Events (version 3.0) and Common Toxicity Criteria (version 3.0).

Pre- and post-vaccine immune assay results (Tumor-specific T-cell Responses) are summarized on a continuous scale as mean.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)

Pre- and post-vaccine immune assay results (Tumor-specific T-cell Responses) are summarized on a continuous scale as mean.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)

To determine the feasibility of this approach, the investigators hypothesize that at least 2/3 of the patients included in the study will be evaluable, meaning that the participants would have received the 3 vaccinations with immunologic outcome parameters measured before and after vaccination. Therefore a maximum of 15 patients would be enrolled in the study to obtain 10 evaluable patients. If after enrolling 15 patients the investigators are unable to obtain 10 evaluable patients, the investigators would consider this approach not feasible.

Time frame: Through enrollment, approximately 2 years

Patients with evidence of evaluable enhancing disease on contrast-enhanced MRI performed within four weeks of study entry will be evaluated for response rate. Patients will be evaluated for objective tumor assessments by gadolinium-enhanced magnetic resonance imaging (Gd-MRI). Comparisons of objective assessments, excluding progressive disease, are based upon major changes in tumor size on the Gd-MRI compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with volumetric analysis.

Time frame: baseline and 4 weeks

Overall survival will also be followed. Survival will be assessed from the date of surgery to the date of patient death, due to any cause, or to the last date the patient was known to be alive.

Time frame: Approximately 42 months

Population: There were 4 patients alive when data collection ended, including the patient the longest overall survival.

Pre- and post-vaccine immune assay results (Tumor-specific T-cell Responses) are summarized on a continuous scale as median. IFN = interferon.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)

Pre- and post-vaccine immune assay results (Tumor-specific T-cell Responses) are summarized on a continuous scale as median.

Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)

Progression-free survival will be assessed for each patient as the time from surgery until the patient reaches objective disease progression by MRI criteria. Death will be regarded as a progression event in those patients that die before disease progression. Patients without documented objective progression at the time of the analysis will be censored at the date of their last objective tumor assessment. Since disease free survival and overall survival are secondary endpoints all patients will be followed until death or for a period of 5 years following enrollment.

Time frame: Approximately 42 months