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

Dartmouth-Hitchcock Medical Center11 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Multiforme

Interventions

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

RT is standard of care (SOC) post surgery

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Outcomes

Primary Outcomes

Tumor-specific Cytotoxic T-cell Response

MRI \& pheresis post vaccine

Time frame: Day 42

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Approximately 42 months

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

Data from ClinicalTrials.gov

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Vaccine given cervical lymphnode injection 3 times every other week

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

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.

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

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).

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.