Adjuvant dendritic-cell immunotherapy plus temozolomide following surgery and chemoradiation in patients with newly diagnosed glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antwerp University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

1 Apr 2016 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515291-13-00

EudraCT number

2014-001098-15

ClinicalTrials.gov

NCT02649582

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine the overall survival (OS) and progression-free survival (PFS) of patients with newly diagnosed glioblastoma when autologous Wilms' tumor 1 mRNA-loaded dendritic-cell vaccination is added to adjuvant temozolomide maintenance treatment following (sub)total resection and temozolomide-based chemoradiation.

Secondary objectives 1

1. To evaluate the feasibility, safety, and immunogenicity of combining autologous dendritic-cell vaccination with standard adjuvant treatment of patients with newly diagnosed glioblastoma following (sub)total resection and temozolomide-based chemoradiation.

Conditions and MedDRA coding

Glioblastoma grade IV

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Newly diagnosed, histologically verified glioblastoma (WHO grade IV)
2. Aged ≥ 18 years
3. Total or subtotal resection: (A) Total resection = macroscopic complete resection as assessed by the neurosurgeon and absence of any residual contrast-enhancing mass on post-operative (≤ 72h) brain MRI (B) Subtotal resection = macroscopic complete resection as assessed by the neurosurgeon, but with residual contrast-enhancement ≤ 2 cm³ on post-operative (≤ 72h) brain MRI
4. Signed informed consent
5. Willing and able to comply with the protocol as judged by the Investigator
6. Estimated to start with chemoradiation ≥ 28 days and ≤ 49 days following surgical resection
7. Fit to undergo: leukapheresis, chemoradiation, chemotherapy and immunotherapy
8. No corticosteroid treatment ≤ 1 week before apheresis
9. WHO performance status ≤ 2
10. Life expectancy ≥ 3 months as estimated by the Investigator

Exclusion criteria 8

1. 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
2. Prior radiation or chemotherapy
3. Any pre-existing contraindication for temozolomide treatment
4. Any pre-existing contraindication for contrast-enhanced brain MRI
5. Pregnant or breast-feeding
6. Documented immune deficiency or systemic immune-suppressive treatment
7. Known positive viral serology for HIV, HBV, HCV, or syphilis
8. 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 1

1. Overall survival (OS) and progression-free survival (PFS)

Secondary endpoints 3

1. Feasibility will be assessed based on the number of (A) patients in the intention-to-treat (ITT) population that had a successful leukapheresis (B) patients in the ITT population that had production of qualified (phenotypic and functional requirements) vaccines (C) efficacy evaluable patients in the ITT population (D) patients with 3-weekly DC vaccine administration following chemoradiation and additional DC vaccination at day 21 of each maintenance chemotherapy cycle in the ITT population
2. Safety will be assessed based on adverse event frequency (scored according to the latest version of the National Cancer Institute Common Terminology Criteria for Adverse Events) in the safety population
3. Immunogenicity will be assessed based on ex vivo immune responses of all patients of the immunogenicity population

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 3 files

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

Application history

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