Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme
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|ClinicalTrials.gov Identifier: NCT00323115|
Recruitment Status : Completed
First Posted : May 9, 2006
Results First Posted : September 26, 2012
Last Update Posted : October 10, 2018
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|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Biological: Autologous Dendritic Cell Drug: Temozolomide Procedure: Radiotherapy Biological: Dendritic Cell Vaccine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Feasibility Study of Adjuvant Intra-Nodal Autologous Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme|
|Study Start Date :||May 2006|
|Actual Primary Completion Date :||April 2008|
|Actual Study Completion Date :||July 2013|
Biological: Autologous Dendritic Cell
Vaccine given by cervical lymph node injection 3 times every other week
Radiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC
RT is standard of care (SOC) post surgery
Biological: Dendritic Cell Vaccine
Vaccine given cervical lymphnode injection 3 times every other week
- Tumor-specific Cytotoxic T-cell Response [ Time Frame: Day 42 ]MRI & pheresis post vaccine
- Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination [ Time Frame: Until death or approximately 24 months after diagnosis ]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.
- Number of Participants With Evaluable Data: Feasibility of Vaccination [ Time Frame: Through enrollment, approximately 2 years ]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 (PFS) [ Time Frame: Approximately 42 months ]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.
- Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment [ Time Frame: baseline and 4 weeks ]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 Duration: Efficacy Parameters [ Time Frame: Approximately 42 months ]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.
- Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Median [ Time Frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination). ]Pre- and post-vaccine immune assay results (Tumor-specific T-cells ) are summarized on a continuous scale as median.
- Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Median [ 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.
- Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Median [ 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.
- Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Mean [ Time Frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination) ]Pre- and post-vaccine immune assay results (Tumor-specific T-cells ) are summarized on a continuous scale as mean.
- Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- 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 median. IFN = interferon.
- Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - 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.
- Evaluation of T Cell Characteristics [ Time Frame: Before starting radiation/Temozolomide and at Day 7 and Day 42. ]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.
- Immunohistochemistry [ Time Frame: Approximately 42 months ]
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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Histologically proven GBM with central pathology review at Dartmouth-Hitchcock Medical Center (DHMC)
- Tumor specimen obtained at the time of surgery adequate for vaccination
- 18 years of age or older
- Karnofsky Performance Status 60% or greater
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10 9th/L
- Platelets greater than or equal to 100 x 10 9th/L
- Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) less than or equal to 5 times the upper limits of normal (ULN)
- Total bilirubin less than or equal to 1.5 times ULN
- Serum creatinine less than or equal to 1.5 times ULN, OR estimated creatinine clearance greater than or equal to 60 mL/min
- No known immunosuppression other than chemo-related
- Negative HIV serologies
- No evidence of acute or chronic hepatitis on standard hepatitis C and B screening tests
- No chemotherapy within four weeks prior to leukapheresis
- Radiotherapy at outside institution is permitted if tissue was obtained at time of surgery at DHMC and patient is willing to follow-up per protocol
- Off steroids for at least two weeks before leukapheresis
- No second malignancies except non-melanoma skin cancer, and non-invasive cancer such at cervical CIS, superficial bladder cancer or breast CIS
- Negative serum or urine pregnancy test for women of childbearing potential
- No serious uncontrolled medical disorder or active infection
- All patients must give informed consent
- No history of clinical evidence of active autoimmune disease
- Invasive cancers in the past 5 years
- Rheumatologic/autoimmune disease
- Pregnancy or unwillingness to remain on acceptable form of birth control during study
- Major cardiac, pulmonary, or other systemic disease; viral hepatitis; HIV infection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00323115
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Camilo E. Fadul, MD||Dartmouth-Hitchcock Medical Center|
|Responsible Party:||Dartmouth-Hitchcock Medical Center|
|Other Study ID Numbers:||
|First Posted:||May 9, 2006 Key Record Dates|
|Results First Posted:||September 26, 2012|
|Last Update Posted:||October 10, 2018|
|Last Verified:||October 2018|
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action