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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Autologous Dendritic Cell

Temozolomide

Radiotherapy

Dendritic Cell Vaccine

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring immunotherapy, cancer vaccine, glioblastoma multiforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Dartmouth-Hitchcock Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccine

Arm Description

Outcomes

Primary Outcome Measures

Tumor-specific Cytotoxic T-cell Response

MRI & pheresis post vaccine

Secondary Outcome Measures

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

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

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)

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

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

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

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

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT00323115

First Posted

May 4, 2006

Last Updated

October 9, 2018

Sponsor

Dartmouth-Hitchcock Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00323115

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

May 2006 (undefined)

Primary Completion Date

April 2008 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dartmouth-Hitchcock Medical Center

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

immunotherapy, cancer vaccine, glioblastoma multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vaccine

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Autologous Dendritic Cell

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Radiotherapy

Intervention Description

RT is standard of care (SOC) post surgery

Intervention Type

Biological

Intervention Name(s)

Dendritic Cell Vaccine

Intervention Description

Vaccine given cervical lymphnode injection 3 times every other week

Primary Outcome Measure Information:

Title

Tumor-specific Cytotoxic T-cell Response

Description

MRI & pheresis post vaccine

Time Frame

Day 42

Secondary Outcome Measure Information:

Title

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

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

Title

Number of Participants With Evaluable Data: Feasibility of Vaccination

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

Title

Progression Free Survival (PFS)

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

Title

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

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

Title

Overall Survival Duration: Efficacy Parameters

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

Title

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

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).

Title

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

Description

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

Time Frame