Adjuvant dendritic cell immunotherapy complementing conventional therapy for pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antwerp University Hospital

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04], Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

6 Oct 2021 → 31 Aug 2025

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515295-12-00

EudraCT number

2020-004125-23

ClinicalTrials.gov

NCT04911621

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

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 objectives 3

1. To assess indicators of clinical activity of vaccination with WT1-targeted DC in pediatric patients with HGG and DIPG
2. To determine the in vivo immunogenicity of WT1-targeted DC vaccinations in pediatric patients with HGG and DIPG
3. To document and characterize changes in patient- and proxy-reported general and disease-specific quality of life

Conditions and MedDRA coding

High-grade glioma (HGG)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.)
2. Aged ≥ 12 months and < 18 years at the time of signing the informed consent
3. Body weight ≥ 10 kg
4. Lansky score (for patients < 16 years) or Karnofsky score (for patients ≥ 16 years) of ≥ 50
5. Reasonable life expectancy ≥ 8 weeks, as estimated by the treating physician
6. 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)
7. 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
8. Willing and able to comply with the protocol, as judged by the treating physician
9. 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

Exclusion criteria 6

1. Use of any investigational agents ≤ 4 weeks before the planned day of leukapheresis
2. Concomitant malignancy or history of another malignancy (unless the Investigator rationalizes otherwise)
3. Known concomitant presence of any active immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo
4. Any pre-existing contra-indication for contrast-enhanced MRI
5. Pregnant or breastfeeding
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Feasibility, based on the proportion of (A) patients in the intention-to-treat (ITT) population that had successful leukapheresis, (B) patients in the ITT population that had successful vaccine production (i.e. production of 9 or more vaccines meeting quality control requirements), (C) patients in the ITT population who complete the study treatment schedule (i.e. from leukapheresis until administration of the 9th vaccine), (D) efficacy evaluable patients in the ITT population
2. Safety: Occurrence of AEs and SAEs during DC vaccine administration and follow-up period (A) Proportion of patients of the safety population that experienced (S)AEs possibly, probably or definitely related to DC vaccination, (B) Number and grade of (S)AEs in the safety population

Secondary endpoints 3

1. Indicators of clinical activity: (A) Best overall response, (B) Progression free survival, (C) Overall survival
2. Immunogenicity, including, but not limited to, the following measures of (anti-tumor) immune responses: (A) Functional WT1-specific T cell responses, (B) Occurrence of WT1-specific CD8+ T cells, (C) Functional WT1-specific T cell responses
3. Quality of life: (A) How patients experience different phases of the study treatment schedule, (B) How patient- and proxy-reported disease-related symptoms evolve over time during the study, (C) How patient- and proxy-reported general quality of life evolves over time during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antwerp University Hospital

Sponsor organisation

Antwerp University Hospital

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Public contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications