E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Childhood high-grade glioma and diffuse intrinsic pontine glioma |
hooggradige gliomen en diffuse intrinsieke gliomen van de pons bij kinderen |
|
E.1.1.1 | Medical condition in easily understood language |
Children and adolescents with brain (stem) tumors |
Kinderen en jongeren met hersen- en hersenstamtumoren |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006143 |
E.1.2 | Term | Brain stem glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080666 |
E.1.2 | Term | Diffuse intrinsic pontine glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
- 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
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 18 years at the time of signing the informed consent - Body weight ≥ 10 kg - Lansky score (for patients < 16 years) or Karnofsky score (for patients ≥ 16 years) of ≥ 50 - Reasonable life expectancy ≥ 8 weeks, as estimated by the treating physician - Adequate hematological blood values and sufficient recovery from treatment-related toxicities (> 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. |
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | 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
|
|
E.5.1.1 | 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. |
|
E.5.2 | 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
|
|
E.5.2.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase I - safety/feasibility |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study will occur when all enrolled patients have reached 90 days of follow-up after final DC vaccine administration or 24 months after study entry, whichever occurs later. Based on the anticipated accrual period of 36 months, the study is estimated to last approximately 72 months. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |