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NCT04911621

PHASE1/PHASE2

Adjuvant Dendritic Cell Immunotherapy for Pediatric Patients With High-grade Glioma or Diffuse Intrinsic Pontine Glioma

Sponsor: University Hospital, Antwerp

View on ClinicalTrials.gov

Summary

Childhood aggressive gliomas are rare brain tumors with very poor prognosis. Due to the tumor's location and infiltrative nature, surgical removal is not always possible, and even when resection is performed and combined with chemo- and/or radiotherapy, tumor cells frequently persist, eventually giving rise to tumor recurrence. A promising strategy to eradicate persisting tumor cells is vaccination with dendritic cells (DC). DC are immune cells that play an important role in organizing the body's defense against cancer. The goal of DC vaccination is to activate these natural anti-tumor defense mechanisms to delay or prevent tumor progression or recurrence. Previous clinical studies have demonstrated that DC vaccination is well-tolerated, safe and capable of eliciting tumorspecific immunity. A clinical study including 10 pediatric patients (aged ≥ 12 months and \< 18 years at the time of signing the informed consent) with brain (stem) tumors is initiated at the Antwerp University Hospital to investigate intradermal vaccination with WT1 mRNA-loaded autologous monocyte-derived DCs, either combined with first-line chemoradiation treatment or administered as adjuvant therapy following previous therapies. The general objective of this phase I/II clinical study is (1) to demonstrate that WT1-targeted DC vaccine production and administration in pediatric patients with HGG and DIPG, either combined with first-line chemoradiation treatment or administered as adjuvant therapy following previous therapies, is feasible and safe, (2) to study vaccine-induced immune responses, (3) to document patients' quality of life and clinical outcome for comparison with current patients' outcome allowing indication of the added value.

Official title: Adjuvant Dendritic Cell Immunotherapy Complementing Conventional Therapy for Pediatric Patients With High-grade Glioma and Diffuse Intrinsic Pontine Glioma

Key Details

Gender

All

Age Range

12 Months - 17 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2021-09-10

Completion Date

2027-06-01

Last Updated

2024-05-08

Healthy Volunteers

Conditions

High Grade Glioma Diffuse Intrinsic Pontine Glioma

Interventions

BIOLOGICAL

Dendritic cell vaccination + temozolomide-based chemoradiation

1. Leukocyte apheresis (before chemoradiation): for dendritic cell (DC) vaccine production. 2. Chemoradiation (1st part standard treatment, initiated as soon as the patient's hematological blood values are adequate after apheresis, but no later than 6 weeks after surgery or confirmed diagnosis): 1.8 Gy once daily 5 days/week for 6 weeks with 90 mg/m² temozolomide daily from the first until the last day of radiotherapy. 3. Induction immunotherapy: intradermal vaccination with autologous Wilms' tumor-1 (WT1) mRNA-loaded DCs weekly (-1 day, +2 days) for 3 weeks, starting ≥ 1 week after radiotherapy. 4. Chemo-immunotherapy: 150-200 mg/m²/d temozolomide days 1-5 every 28 days +/- 3 days (max. 6 months, 2nd part standart treatment) starting ≥3 days after the third vaccine of the induction immunotherapy + DC vaccination on day 21±3 days of every 28-day cycle.

BIOLOGICAL

Dendritic cell vaccination +- conventional next-line treatment

1. Leukocyte apheresis (upon recovery of hematological blood values following previous anti-glioma treatments and ≥ 4 weeks after the last dose of any investigational agent): for DC vaccine production. 2. Induction immunotherapy: intradermal vaccination with autologous WT1 mRNA-loaded DCs weekly (-1 day, +2 days) for 3 weeks, starting ≥ 4 weeks after apheresis. 3. Booster immunotherapy: 6 DC booster vaccinations administered at regular intervals (+- 4 weeks), starting ≥ 3 weeks after the last induction vaccine. 4. (Optional) Concomitant conventional anti-glioma treatment: The decision to continue or re-initiate conventional anti-glioma treatment, and, if applicable, its dose and scheme, are at the Investigator's discretion and will depend on the patient's previous treatment scheme and condition.

Inclusion Criteria: * Diagnosis of * High grade glioma (WHO grade III or IV), histologically verified * Diffuse Intrinsic Pontine Glioma, 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 * Written informed consent of parents or legal guardian. Written informed consent 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. 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

Locations (1)

Unitversity Hospital Antwerp

Edegem, Belgium