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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00323115
Recruitment Status : Completed
First Posted : May 9, 2006
Results First Posted : September 26, 2012
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma Multiforme
Interventions Biological: Autologous Dendritic Cell
Drug: Temozolomide
Procedure: Radiotherapy
Biological: Dendritic Cell Vaccine
Enrollment 11
Recruitment Details Between May 2006 and February 2008, 60 patients were diagnosed with GBM at our institution. Of 11 patients who entered the study, 1 had a seizure with neurologic deterioration several weeks after leukapheresis and did not receive any DC vaccinations.
Pre-assignment Details  
Arm/Group Title Vaccine
Hide Arm/Group Description 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
Period Title: Vaccine Administration
Started 11
Completed 10
Not Completed 1
Reason Not Completed
Adverse Event             1
Period Title: Adjuvant Therapy & Survival Follow-Up
Started 10
Completed 2
Not Completed 8
Reason Not Completed
Death             8
Arm/Group Title Vaccine
Hide Arm/Group Description 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
Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
<=18 years
0
   0.0%
Between 18 and 65 years
6
  54.5%
>=65 years
5
  45.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants
63.273  (9.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
6
  54.5%
Male
5
  45.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants
11
1.Primary Outcome
Title Tumor-specific Cytotoxic T-cell Response
Hide Description MRI & pheresis post vaccine
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received all 3 vaccine administrations were used in this data analysis.
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: 10^9 cells/L
No. CD4+
0.496
(0.198 to 0.921)
No. CD8+
0.4836
(0.135 to 0.976)
2.Secondary Outcome
Title Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: attributable adverse events
1
3.Secondary Outcome
Title Number of Participants With Evaluable Data: Feasibility of Vaccination
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
10
 100.0%
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: Months
9.5
(5 to 41)
5.Secondary Outcome
Title Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
6.Secondary Outcome
Title Overall Survival Duration: Efficacy Parameters
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
There were 4 patients alive when data collection ended, including the patient the longest overall survival.
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: Months
28
(15 to 44)
7.Secondary Outcome
Title Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Median
Hide Description 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).
Hide Outcome Measure Data
Hide Analysis Population Description
proportion of cells responding to GBM; GBM = glioblastoma multiforme
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: proportion of cells
Precursor frequency of CD4+ T cells
0.003
(0.0003 to 0.03)
0.01
(0.0004 to 0.04)
Precursor frequency of CD8+ T cells
0.001
(0.0003 to 0.003)
0.001
(0.0002 to 0.01)
8.Secondary Outcome
Title Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Median
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: percentage of cells
Percentage of CD4+ proliferating and IFN
0.15
(0.004 to 1.96)
0.25
(0.05 to 5.05)
Percentage of CD8+ proliferating and IFN
0.27
(0.01 to 1.45)
0.25
(0.04 to 4.29)
9.Secondary Outcome
Title Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Median
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: spots
0
(0 to 14)
0
(0 to 341)
10.Secondary Outcome
Title Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Mean
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
proportion of cells responding to GBM; GBM = glioblastoma multiforme
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: proportion of cells
Precursor frequency of CD4+ T cells 0.005  (0.009) 0.01  (0.01)
Precursor frequency of CD8+ T cells 0.001  (0.0008) 0.003  (0.004)
11.Secondary Outcome
Title Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Mean
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: percentage of cells
Percentage of CD4+ proliferating and IFN 0.38  (0.62) 0.88  (1.55)
Percentage of CD8+ proliferating and IFN 0.45  (0.48) 0.92  (1.37)
12.Secondary Outcome
Title Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Mean
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-Vaccine Post-Vaccine
Hide Arm/Group Description:
[Not Specified]
Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: spots
1.40  (4.43) 44.2  (105.8)
13.Secondary Outcome
Title Evaluation of T Cell Characteristics
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vaccine - Before Starting Radiation/TMZ Vaccine - First Leukapheresis Vaccine - Second Leukapheresis
Hide Arm/Group Description:
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
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
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
Overall Number of Participants Analyzed 10 10 10
Mean (Standard Deviation)
Unit of Measure: percentage of cells
% of CD3+/CD8+/CD45RO+ (memory T-cells) 30.8  (11.2) 25.8  (9.8) 19.3  (7.0)
% CD3+/CD8+/CD28- (CD8 suppressor T cell phenotype 34.6  (21.0) 30.5  (18.7) 23.7  (7.2)
%CD4+/CD25+ cells 14.9  (6.8) 14.1  (5.6) 11.8  (6.1)
% of are T regulatory cells (TREG) 4.0  (2.0) 3.5  (1.9) 1.2  (0.7)
14.Secondary Outcome
Title Immunohistochemistry
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Vaccine
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From Baseline through 30 days after last administration of vaccine.
Adverse Event Reporting Description Participants who started in the "Adjuvant Therapy" Period were assessed for Other/Non-Serious Adverse Events
 
Arm/Group Title Vaccine
Hide Arm/Group Description 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
All-Cause Mortality
Vaccine
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Vaccine
Affected / at Risk (%) # Events
Total   0/11 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vaccine
Affected / at Risk (%) # Events
Total   1/10 (10.00%)    
Musculoskeletal and connective tissue disorders   
Pain, neck, unilateral, Grade 2  1  1/10 (10.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v3.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Camilo Fadul
Organization: Dartmouth-Hitchcock Medical Center
Phone: 603-653-6312
EMail: camilo.e.fadul@hitchcock.org
Layout table for additonal information
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00323115    
Other Study ID Numbers: D0536
First Submitted: May 4, 2006
First Posted: May 9, 2006
Results First Submitted: August 24, 2012
Results First Posted: September 26, 2012
Last Update Posted: October 10, 2018