Clinical trial NCT02649582: Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients
Official title: Adjuvant Dendritic-Cell Immunotherapy Plus Temozolomide Following Surgery and Chemoradiation in Patients With Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme of Brain
Keywords: Dendritic cells
Chemoimmunotherapy
Adjuvant therapy
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2016-01-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Secondary outcomes:
measure: Number of glioblastoma patients post surgical resection with feasible and safe DC vaccine production
timeFrame: Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)
measure: Feasibility of DC vaccine administration to glioblastoma patients combined with chemotherapy
timeFrame: Upon maintenance chemotherapy treatment (i.e. +/- 12 weeks post leukapheresis)
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
measure: Immunological responses to the DC vaccine
timeFrame: At first DC vaccination + day 1 of first and fourth temozolomide treatment cycles
measure: Objective clinical responses by tumor evaluation (clinical efficacy)
timeFrame: Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Other outcomes:
measure: General and disease-specific quality of life
timeFrame: Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
Study officials:
affiliation: Antwerp University Hospital, Division of Hematology and Center for Cell Therapy and Regenerative Medicine
name: Zwi N Berneman, MD, PhD
role: STUDY_DIRECTOR
affiliation: Antwerp University Hospital (UZA), Division of Oncology
name: Marika Rasschaert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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