Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients
In this phase I/II trial, the primary objective is to determine overall and progression-free survival of patients with newly diagnosed glioblastoma when autologous Wilms' tumor 1 (WT1) messenger (m)RNA-loaded dendritic cell (DC) vaccination is added to adjuvant temozolomide maintenance treatment following (sub)total resection and temozolomide-based chemoradiation.
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
|Eligible Ages||18 Years and Over|
Inclusion Criteria:- Newly diagnosed, histologically verified glioblastoma (WHO grade IV) - Aged ≥ 18 years - Total or subtotal resection: - Total resection: macroscopic complete resection as assessed by the neurosurgeon and absence of any residual contrast-enhancing mass on post-operative (≤ 72h) brain MRI - Subtotal resection: macroscopic complete resection as assessed by the neurosurgeon, but with residual contrast-enhancement ≤ 2 cm³ on post-operative (≤ 72h) brain MRI - Signed informed consent - Willing and able to comply with the protocol as judged by the Investigator - Estimated to start with chemoradiation ≥ 28 days and ≤ 49 days following surgical resection - Adequate hematologic, renal, and hepatic function at time of screening: - Hemoglobin ≥ 10 g/dL (transfusion is allowed to maintain or exceed this level) - Monocyte count (Mo) ≥ 0.2 x 10^9/L - Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L - Platelet count (PLT) ≥ 100 x 10^9/L - Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) - Liver-function values < 3 x ULN - No corticosteroid treatment ≤ 1 week before apheresis - WHO performance status ≤ 2 - Life expectancy ≥ 3 months as estimated by the Investigator
Exclusion Criteria:- History of another malignancy, except for adequately controlled basal cell skin carcinoma, squamous skin carcinoma, or carcinoma in situ of the uterine cervix - Prior radiation or chemotherapy - Any pre-existing contraindication for temozolomide treatment - Any pre-existing contraindication for contrast-enhanced brain MRI - Pregnant or breast-feeding - Documented immune deficiency or systemic immune-suppressive treatment - Positive viral serology for HIV, HBV, HCV, or syphilis at time of screening - Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of the vaccine, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 0: Exploratory study involving very limited human exposure to the drug to determine whether a drug is modulating its target.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
|Phase 1/Phase 2|
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|University Hospital, Antwerp|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Glioblastoma Multiforme of Brain|
Glioblastoma multiforme (GBM), a microscopically infiltrative disease, is the most common malignant brain tumor worldwide. Despite optimized standard of care treatment median survival and prognosis remain poor with a median survival of only 15% and five year survival after diagnosis of 5%. In this single arm single centre phase I/II trial the investigators will determine the overall and progression free survival of patients with newly diagnosed GBM when autologous WT1 mRNA loaded dendritic cell vaccination is added to standard of care treatment. During two years of recruitment the investigators will include 20 patients with newly diagnosed, histologically verified glioblastoma (WHO grade IV) who have received a total or subtotal resection of the tumor. Patients who underwent prior radiation or chemotherapy or with a history of other malignancy will be excluded. In addition to standard of care consisting of adjuvant chemoradiation with temozolomide and temozolomide maintenance patients will receive an intradermal vaccination with autologous WT1 mRNA-loaded dendritic cells commencing 1 week after radiotherapy. The dendritic cell therapy product will be generated and administered in the Antwerp University Hospital, more specifically the Center for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed by Prof. Zwi Berneman. Recruitment will begin in December 2015. After 2 years of follow up overall and progression free survival analysis will be performed and this will be compared with the published data of standard of care treatment without vaccination. In addition the investigators will look for feasibility, incidence of adverse events and immunogenicity.
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