Childhood high-grade glioma and diffuse intrinsic pontine glioma MedDRA version: 20.0 Level: LLT Classification code 10046859 Term: Vaccination System Organ Class: 100000004865 MedDRA version: 20.0 Level: PT Classification code 10006143 Term: Brain stem glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10080666 Term: Diffuse intrinsic pontine glioma System Organ Class: 10029104 - Neopla
Conditions
Interventions
Product Name: cryopreserved Wilms' tumor 1 (WT1) mRNA-electroporated dendritic cells
Product Code: WT1 EP DC
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Wilms' tumor 1 (WT1) mRN
Sponsors
Antwerp University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of HGG (WHO grade III or IV, histologically verified) or DIPG (verified by radiologic criteria (magnetic resonance imaging (MRI)) or by histology. A biopsy is not required but recommended.) - Aged = 12 months and grade 1) following previous anti-glioma treatments, as judged by the treating physician (applies to stratum B only). - Written informed consent of parents or legal guardian and of patients aged 12 years or older. Written informed consent of patients younger than 12 years is optional. - Willing and able to comply with the protocol, as judged by the treating physician - Female patients of child bearing potential must have a negative serum or urine pregnancy test at the time of screening. Female patients of child bearing potential and male patients must agree to use effective contraception before, during and for at least hundred days after the last study treatment administration. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until at least hundred days after the last study treatment administration. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Use of any investigational agents = 4 weeks before the planned day of leukapheresis. - Concomitant malignancy or history of another malignancy (unless the Investigator rationalizes otherwise) - Known concomitant presence of any active immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo - Any pre-existing contra-indication for contrast-enhanced MRI - Pregnant or breastfeeding - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the feasibility of WT1-targeted DC vaccine production and administration in pediatric patients with HGG and DIPG, either in combination with first-line chemoradiation treatment or as adjuvant therapy following previous therapies, and to investigate the resulting safety profile.;Secondary Objective: - To assess indicators of clinical activity of vaccination with WT1-targeted DC in pediatric patients with HGG and DIPG - To determine the in vivo immunogenicity of WT1-targeted DC vaccinations in pediatric patients with HGG and DIPG - To document and characterize changes in patient- and proxy-reported general and disease-specific quality of life ;Primary end point(s): (i) Feasibility - Proportion of patients in the intention-to-treat (ITT) population that had successful leukapheresis - Proportion of patients in the ITT population that had successful vaccine production (i.e. production of 9 or more vaccines meeting quality control requirements) - Proportion of patients in the ITT population who complete the study treatment schedule (i.e. from leukapheresis until administration of the 9th vaccine) - Proportion of efficacy evaluable patients in the ITT population (ii) Safety Occurrence of AEs and SAEs during DC vaccine administration and follow-up period: - Proportion of patients of the safety population that experienced (S)AEs possibly, probably or definitely related to DC vaccination - Number and grade of (S)AEs in the safety population ;Timepoint(s) of evaluation of this end point: At end of study (i.e. when all patients have reached 90 days after final DC vaccine administration or 24 months after study entry (whichever occurs later)) data for feasibility and safety will be evaluated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (i) Indicators of clinical activity: - Best overall response - Progression free survival - Overall survival (ii) Immunogenicity The immunogenicity endpoints include, but are not limited to, the following measures of (anti-tumor) immune responses: - Functional WT1-specific T cell responses - Occurrence of WT1-specific CD8+ T cells - Functional WT1-specific T cell responses (iii) Quality of life - How patients experience different phases of the study treatment schedule - How patient- and proxy-reported disease-related symptoms evolve over time during the study - How patient- and proxy-reported general quality of life evolves over time during the study ;Timepoint(s) of evaluation of this end point: At end of study (i.e. when all patients have reached 90 days after final DC vaccine administration or 24 months after study entry (whichever occurs later)) data for clinical activity, immunogenicity and quality of life questionnaires will be evaluated. | — |
Countries
Belgium
Contacts
Public ContactCCRG
Antwerp University Hospital
Outcome results
None listed