Ignite Creation Date:
2024-05-06 @ 4:13 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04911621
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-08
First Post:
2021-04-30
Brief Title:
Adjuvant Dendritic Cell Immunotherapy for Pediatric Patients With High-grade Glioma or Diffuse Intrinsic Pontine Glioma
Sponsor:
University Hospital Antwerp
Organization:
University Hospital Antwerp
Study Overview
Official Title:
Adjuvant Dendritic Cell Immunotherapy Complementing Conventional Therapy for Pediatric Patients With High-grade Glioma and Diffuse Intrinsic Pontine Glioma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ADDICT-pedGLIO
Brief Summary:
Childhood aggressive gliomas are rare brain tumors with very poor prognosis Due to the tumors location and infiltrative nature surgical removal is not always possible and even when resection is performed and combined with chemo- andor 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 bodys 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 III 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
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 III 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
Detailed Description:
1 Overview of the study treatment scheme
11 Newly diagnosed HGG and DIPG patients stratum A
Patients will be screened and registered in the study following diagnosis which is based on either histological confirmation or radiographic criteria Maximal safe resection prior to study entry is strongly recommended but not required
Eligible patients will undergo leukapheresis prior to temozolomide-based chemoradiation and subsequent chemo-immunotherapy with maintenance temozolomide and autologous WT1 mRNA-loaded DC vaccination Chemoradiation with subsequent maintenance temozolomide is considered best available treatment and therefore not considered investigational The investigational treatment ie adjuvant DC vaccination is administered in 2 phases
an induction phase consisting of 3 weekly -1 day 2 days DC vaccines which is initiated after chemoradiation but before maintenance temozolomide therapy and
a booster phase consisting of 6 4-weekly 3 days DC vaccines which are administered during temozolomide maintenance cycles
12 Non-treatment naïve HGG and DIPG patients stratum B
Patients who have undergone previous anti-glioma treatments can be included in the study provided they are eligible according to the in- and exclusion criteria
The decision to start continue or re-initiate conventional anti-glioma treatment including radio- andor chemotherapy and if applicable the treatment dose and scheme are at the Investigators discretion The backbone DC immunotherapy scheme for the induction and booster phase will be maintained with minor modifications
during the induction phase 3 DC vaccines will be administered on a weekly -1 day 2 days basis
during the booster phase 6 DC vaccines will be administered at regular intervals It is recommended that the time between subsequent vaccinations is no longer than 4 weeks
13 Continuation of DC vaccination
While the study treatment schedule consists of 9 DC vaccinations ie 3 induction and 6 booster vaccines continuation of DC vaccination after the booster phase is allowed on the conditions that 1 the Investigator judges that the participants clinical situation justifies additional vaccinations 2 consent for continuation of DC vaccination of the parentsguardian and the participant if aged 12 years or older has been obtained and 3 residual vaccine aliquots are available
2 Response assessment
Disease evolution will be assessed radiologically according to the Response Assessment in Neuro-Oncology RANO criteria In addition blood samples will be collected for immunomonitoring purposes on the day of the first fourth and seventh DC vaccine Tumor resection or biopsy specimens if available will be used for local immunological and biomarker analysis At regular time points throughout the study scheme parents and participants will be asked to fill out questionnaires on general and disease-specific quality-of-life as well as on executive function
3 Follow-up
Patients will be followed-up until 90 days after administration of the final DC vaccine or 24 months after study entry whichever occurs later
11 Newly diagnosed HGG and DIPG patients stratum A
Patients will be screened and registered in the study following diagnosis which is based on either histological confirmation or radiographic criteria Maximal safe resection prior to study entry is strongly recommended but not required
Eligible patients will undergo leukapheresis prior to temozolomide-based chemoradiation and subsequent chemo-immunotherapy with maintenance temozolomide and autologous WT1 mRNA-loaded DC vaccination Chemoradiation with subsequent maintenance temozolomide is considered best available treatment and therefore not considered investigational The investigational treatment ie adjuvant DC vaccination is administered in 2 phases
an induction phase consisting of 3 weekly -1 day 2 days DC vaccines which is initiated after chemoradiation but before maintenance temozolomide therapy and
a booster phase consisting of 6 4-weekly 3 days DC vaccines which are administered during temozolomide maintenance cycles
12 Non-treatment naïve HGG and DIPG patients stratum B
Patients who have undergone previous anti-glioma treatments can be included in the study provided they are eligible according to the in- and exclusion criteria
The decision to start continue or re-initiate conventional anti-glioma treatment including radio- andor chemotherapy and if applicable the treatment dose and scheme are at the Investigators discretion The backbone DC immunotherapy scheme for the induction and booster phase will be maintained with minor modifications
during the induction phase 3 DC vaccines will be administered on a weekly -1 day 2 days basis
during the booster phase 6 DC vaccines will be administered at regular intervals It is recommended that the time between subsequent vaccinations is no longer than 4 weeks
13 Continuation of DC vaccination
While the study treatment schedule consists of 9 DC vaccinations ie 3 induction and 6 booster vaccines continuation of DC vaccination after the booster phase is allowed on the conditions that 1 the Investigator judges that the participants clinical situation justifies additional vaccinations 2 consent for continuation of DC vaccination of the parentsguardian and the participant if aged 12 years or older has been obtained and 3 residual vaccine aliquots are available
2 Response assessment
Disease evolution will be assessed radiologically according to the Response Assessment in Neuro-Oncology RANO criteria In addition blood samples will be collected for immunomonitoring purposes on the day of the first fourth and seventh DC vaccine Tumor resection or biopsy specimens if available will be used for local immunological and biomarker analysis At regular time points throughout the study scheme parents and participants will be asked to fill out questionnaires on general and disease-specific quality-of-life as well as on executive function
3 Follow-up
Patients will be followed-up until 90 days after administration of the final DC vaccine or 24 months after study entry whichever occurs later
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None