Glioblastoma MultiformePhase 2NCT00323115
Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme
A Phase 2 study testing Autologous Dendritic Cell, Temozolomide and Radiotherapy in people with Glioblastoma Multiforme, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Autologous Dendritic Cell, Temozolomide and Radiotherapy
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Jul 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: 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.
Read the 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.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Autologous Dendritic Cell, Temozolomide, Radiotherapy, Dendritic Cell Vaccine
- Keywords
- immunotherapy, cancer vaccine, glioblastoma multiforme
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Dendritic CellBiological
Vaccine given by cervical lymph node injection 3 times every other week
TemozolomideDrug
Radiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC
RadiotherapyProcedure or surgery
RT is standard of care (SOC) post surgery
Dendritic Cell VaccineBiological
Vaccine given cervical lymphnode injection 3 times every other week
| Study group | Role | What they receive |
|---|---|---|
| Vaccine | Experimental | Not described Receives: Biological: Autologous Dendritic Cell; Drug: Temozolomide; Procedure: Radiotherapy; Biological: Dendritic Cell Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor-specific Cytotoxic T-cell Response
MRI \& pheresis post vaccine
Measured: Day 42
Secondary outcomes (13)
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.
Measured: Until death or approximately 24 months after diagnosis
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.
Measured: Through enrollment, approximately 2 years
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.
Measured: Approximately 42 months
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.
Measured: baseline and 4 weeks
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.
Measured: Approximately 42 months
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination).
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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.
Measured: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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.
Measured: Before starting radiation/Temozolomide and at Day 7 and Day 42.
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.
Measured: Approximately 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2006 (estimated)
- Study startMay 2006
- Primary completionApr 2008
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Camilo E. Fadul, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00323115
- Sponsor's protocol ID
- D0536
- Status last verified
- Oct 2018
- First submitted
- 4 May 2006
- Last updated
- 10 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21499132
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Feasibility Study of Adjuvant Intra-Nodal Autologous Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00323115
- Acronym / sponsor ID
- D0536
- Conditions
- Glioblastoma Multiforme
- Keywords
- immunotherapy, cancer vaccine, glioblastoma multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- May 2006
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 9 May 2006 (estimated)
- Results
- Posted 26 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaccine | Experimental | Biological: Autologous Dendritic Cell, Drug: Temozolomide, Procedure: Radiotherapy, Biological: Dendritic Cell Vaccine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Dendritic CellVaccine given by cervical lymph node injection 3 times every other week | Biological | Vaccine |
| TemozolomideRadiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC | Drug | Vaccine |
| RadiotherapyRT is standard of care (SOC) post surgery | Procedure or surgery | Vaccine |
| Dendritic Cell VaccineVaccine given cervical lymphnode injection 3 times every other week | Biological | Vaccine |
Primary outcome
Tumor-specific Cytotoxic T-cell Response
Time frame: Day 42
MRI \& pheresis post vaccine
13 secondary outcomes
Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination
Time frame: Until death or approximately 24 months after diagnosis
Number of Participants With Evaluable Data: Feasibility of Vaccination
Time frame: Through enrollment, approximately 2 years
Progression Free Survival (PFS)
Time frame: Approximately 42 months
Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment
Time frame: baseline and 4 weeks
Overall Survival Duration: Efficacy Parameters
Time frame: Approximately 42 months
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).
Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Median
Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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)
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)
Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Mean
Time frame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
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)
Evaluation of T Cell Characteristics
Time frame: Before starting radiation/Temozolomide and at Day 7 and Day 42.
Immunohistochemistry
Time frame: Approximately 42 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21499132Fadul 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camilo E. Fadul, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Dendritic Cell, Temozolomide and Radiotherapy in people with Glioblastoma Multiforme, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor-specific Cytotoxic T-cell Response (time frame: Day 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00323115, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2018.