ClinicalTrials.gov
ClinicalTrials.gov Menu

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

May 4, 2006
May 9, 2006
August 24, 2012
September 26, 2012
October 10, 2018
May 2006
April 2008   (Final data collection date for primary outcome measure)
Tumor-specific Cytotoxic T-cell Response [ Time Frame: Day 42 ]
MRI & pheresis post vaccine
To Determine Whether Intranodal Injection of an Autologous Glioma Lysate-derived Dendritic Cell Vaccine Will Result in a Measurable Tumor-specific Cytotoxic T-cell Response
Complete list of historical versions of study NCT00323115 on ClinicalTrials.gov Archive Site
  • 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.
  • To Determine Feasibility and Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination in This Context
  • To Compare the Progression Free Survival and Overall Survival With Prognostic Matched Historical Controls
  • To Correlate the Immunological Parameters With PFS and Overall Survival
  • To Assess Radiological Response When There is Residual Enhancing Tumor at Baseline MRI
  • In patients who require a second surgical resection, to compare the inflammatory changes in the initial surgical specimen to the post treatment specimen
Not Provided
Not Provided
 
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
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.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Glioblastoma Multiforme
  • Biological: Autologous Dendritic Cell
    Vaccine given by cervical lymph node injection 3 times every other week
  • Drug: Temozolomide
    Radiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC
  • Procedure: Radiotherapy
    RT is standard of care (SOC) post surgery
  • Biological: Dendritic Cell Vaccine
    Vaccine given cervical lymphnode injection 3 times every other week
Experimental: Vaccine
Interventions:
  • Biological: Autologous Dendritic Cell
  • Drug: Temozolomide
  • Procedure: Radiotherapy
  • Biological: Dendritic Cell Vaccine
Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, Szczepiorkowski ZM, Tosteson TD, Rhodes CH, Wishart HA, Lewis LD, Ernstoff MS. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother. 2011 May;34(4):382-9. doi: 10.1097/CJI.0b013e318215e300.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
11
10
July 2013
April 2008   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00323115
D0536
No
Not Provided
Not Provided
Dartmouth-Hitchcock Medical Center
Dartmouth-Hitchcock Medical Center
Not Provided
Principal Investigator: Camilo E. Fadul, MD Dartmouth-Hitchcock Medical Center
Dartmouth-Hitchcock Medical Center
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP