Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Temozolomide

Immunomodulating Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Vaccine given by cervical lymph node injection 3 times every other week

Autologous Dendritic Cell

Radiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC

RT is standard of care (SOC) post surgery

Radiotherapy

Vaccine given cervical lymphnode injection 3 times every other week

Dendritic Cell Vaccine

Camilo E. Fadul, MD

Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme will be treated with radiotherapy/chemotherapy followed by dendritic cell vaccine. Chemotherapy will be administered after three vaccinations for one year or until progression of disease.

Two to six weeks after surgery, patients with newly diagnosed glioblastoma multiforme (GBM) will undergo a six-week course of radiotherapy with concurrent chemotherapy (temozolomide). Between three and seven weeks after completing radiotherapy/chemotherapy, patients will undergo leukapheresis to collect white blood cells. These cells will be grown into dendritic cells, and cultured with tumor cells from the individual patient. Vaccinations will be given every two weeks for a total of three vaccinations. Four weeks after the third vaccination patients will resume chemotherapy for one year or until disease progression.

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

A Phase II Feasibility Study of Adjuvant Intra-Nodal Autologous Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme

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.

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.

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.

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.

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.

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

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

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

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

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

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.

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.

Dartmouth-Hitchcock Medical Center

Participants who started in the "Adjuvant Therapy" Period were assessed for Other/Non-Serious Adverse Events

Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression

Vaccine

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Camilo Fadul

No. CD4+

No. CD8+

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

Tumor-specific Cytotoxic T-cell Response

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).

Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination

Number of Participants With Evaluable Data: Feasibility of Vaccination

Progression Free Survival (PFS)

Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment

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

Overall Survival Duration: Efficacy Parameters

Precursor frequency of CD4+ T cells

Precursor frequency of CD8+ T cells

Pre-Vaccine

Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week

Post-Vaccine

proportion of cells responding to GBM; GBM = glioblastoma multiforme

Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Median

Percentage of CD4+ proliferating and IFN

Percentage of CD8+ proliferating and IFN

Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Median

Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Median

Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Mean

Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Mean

Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Mean

% of CD3+/CD8+/CD45RO+ (memory T-cells)

% CD3+/CD8+/CD28- (CD8 suppressor T cell phenotype

%CD4+/CD25+ cells

% of are T regulatory cells (TREG)

Vaccine - Before Starting Radiation/TMZ

Vaccine - First Leukapheresis

Vaccine - Second Leukapheresis

Evaluation of T Cell Characteristics

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.

Immunohistochemistry

Vaccine Administration

Adjuvant Therapy & Survival Follow-Up

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hormones

Autologous dendritic cells pulsed with prostate cancer antigen and KLH

Autologous dendritic cell

J C W, M.D,Ph.D

This is an open label, Phase I/IIa trial of immunotherapy with CreaVax-PC as treatment in men with hormone-Refractory Metastatic Prostate Cancer.

CreaVax-PC consisted of antigen (PSA, PAP and KLH) primed dendritic cell is an investigational product designed to activate a man's immune response, so they can detect prostate cancer cells and initiate an immune response against prostate cancer antigens.

If patients decide to participate and are eligible, they will be enrolled in the study and will receive active product (CreaVax-PC). In detail, patients will receive CreaVax-PC injection at intervals of 3 weeks, maximum 6 times during 21 weeks. PSA increase rate is a primary evaluation variables and tumor suppression effect is secondary evaluation variables. We also evaluate time to progression, overall survival and immune response.

Autologous Dendritic Cell Therapy for Hormone-Refractory Metastatic Prostate Cancer

A Phase I/IIa Study of Autologous Cell-based Vaccine Therapy With CreaVax-PC in Hormone-Refractory Metastatic Prostate Cancer Patients With PSA Relapse to Evaluate the Safety and Efficacy

PSA response evaluation at 12 weeks and follow up response evaluation at 21 weeks

Clinical course of participants as measured by bone scans and CT

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme	NCT00323115	Glioblastoma Mu...	Autologous Dend... Temozolomide Radiotherapy Dendritic Cell ...	18 Years -	Dartmouth-Hitchcock Medical Center
Autologous Dendritic Cell Therapy for Hormone-Refractory Metastatic Prostate Cancer	NCT01171729	Prostatic Cance...	Autologous dend...	18 Years -	Samsung Medical Center
Autologous Dendritic Cell Therapy for Hormone-Refractory Metastatic Prostate Cancer	NCT01171729	Prostatic Cance...	Autologous dend...	18 Years -	Samsung Medical Center

Spots Global Cancer Trial Database for autologous dendritic cell