Adjuvant Dendritic-Cell Immunotherapy Plus Temozolomide Following Surgery and Chemoradiation in Patients With Newly Diagnosed Glioblastoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- University Hospital, Antwerp
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Overall survival
Study Overview
Brief Summary
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.
Detailed Description
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 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), headed by Prof. Zwi Berneman and the Division of Hematology.
Recruitment began in December 2015 and is intended to continue until the end of 2024 or when 20 patients are enrolled. After a follow-up period (until 90 days after final DC vaccine administration or 24 months after apheresis , whichever occurs later), 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •Fit to undergo: leukapheresis, chemoradiation, chemotherapy and immunotherapy
- •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 or unless the investigator rationalizes otherwise
- •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
- •Known positive viral serology for HIV, HBV, HCV, or syphilis
- •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
Arms & Interventions
Single Arm
Dendritic cell vaccine plus temozolomide chemotherapy
Intervention: Dendritic cell vaccine plus temozolomide chemotherapy (Biological)
Outcomes
Primary Outcomes
Overall survival
Time Frame: Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Patients will be followed for survival, from apheresis (\~ diagnosis), for which the accurate date and reason of death (cancer-related or non-related) will be recorded for every patient.
Secondary Outcomes
- Objective clinical responses by tumor evaluation (clinical efficacy)(Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later)
- Number of participants with adverse events as a measure of safety and tolerability(Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later)
- Number of glioblastoma patients post surgical resection with feasible and safe DC vaccine production(Vaccine production and quality testing (i.e. 4 weeks after leukapheresis))
- Feasibility of DC vaccine administration to glioblastoma patients combined with chemotherapy(Upon maintenance chemotherapy treatment (i.e. +/- 12 weeks post leukapheresis))
- Immunological responses to the DC vaccine(At first DC vaccination + day 1 of first and fourth temozolomide treatment cycles)
Investigators
Zwi Berneman
Full Professor
University Hospital, Antwerp