Ignite Creation Date:
2025-12-25 @ 3:53 AM
Ignite Modification Date:
2025-12-26 @ 2:42 AM
Study NCT ID:
NCT01567202
Status:
UNKNOWN
Last Update Posted:
2020-09-09
First Post:
2012-03-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of DC Vaccination Against Glioblastoma
Sponsor:
Huashan Hospital
Organization:
Study Overview
Official Title:
A Triple-blind Randomized Clinical Study of Vaccination With Dendritic Cells Loaded With Glioma Stem-like Cells Associated Antigens Against Brain Glioblastoma Multiform
Status:
UNKNOWN
Status Verified Date:
2020-09
Last Known Status:
RECRUITING
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:
None
Brief Summary:
This is a Phase II study in a single center to determine the efficacy of autologous dendritic cells (DCs) loaded with autogeneic glioma stem-like cells (A2B5+) administered as a vaccination in adults with glioblastoma multiforme (primary or secondary).
Detailed Description:
Despite the advances in diagnosis and treatment (surgery +radiation +chemotherapy), median survival for patients with newly diagnosed brain glioblastoma multiform (GBM) is about one year, for recurrent GBM is about 4 months. Recently, immunotherapy has emerged as a novel treatment strategy for glioma with improving patient survival. Usually, processed tumor antigens from the patient's own tumor or a peptide vaccine is capable of producing an anti-glioma response. Our previous experiment revealed that the CD133+ tumor stem-like cells associated antigens could elicit highly intensive immune response against human malignant glioma , and in phase I study, we have confirmed that DC vaccine loaded with glioma stem-like cells associated antigens against malignant glioma in recurrent patients was of safety .
Autologous DCs will be obtained from peripheral blood mononuclear cells (PBMCs) from each patient. Stem-like cells associated antigens (SAA) will be prepared with glioma stem-like cells that are harvested from patients with GBM and primary cultured and sorted flowcytometrically and then irradiated. Approximately 4 weeks will be required for vaccine production and the first vaccine administration. Each patient will receive an injection of DCs at his/her assigned dose once every week during the first 6 week. The dose of DCs is defined as 8\~10×10\^6.
Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately, at the present time the majority of clinical trials were in phase I that illustrated the safety. The efficacy of DCs against glioblastoma is still lack of sufficient randomized phase II study. According to our previous phase I study, here we designed this clinical trial in a triple-blind randomized manner to validate the efficacy of DCs vaccination.
Recently，an exploratory randomized phase II clinical trial have been completed （Cancer immunology \&immunotheapy ，2018，1677，1677-1688 ； PubMed ID: 30159779）， 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1wild type (WT) TERTMT patients, DCV treatment significantly prolonged OS (p \< 0.01) and PFS (p = 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment.
In the present study, IDH1WTTERTMT subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy. However，It is noted that IDH1WTTERTMTGBM patients was analysed in a cohort samples which are not randomlized and the present study population is too small to evaluate conclusively demographic criteria for entry and patient recruitment. the results of the present study should be confirmed in a random cohort of IDH1WTTERTMT GBM patients. Accordingly , we made some modifications to the original plan, and are currently recruiting new participants.
Autologous DCs will be obtained from peripheral blood mononuclear cells (PBMCs) from each patient. Stem-like cells associated antigens (SAA) will be prepared with glioma stem-like cells that are harvested from patients with GBM and primary cultured and sorted flowcytometrically and then irradiated. Approximately 4 weeks will be required for vaccine production and the first vaccine administration. Each patient will receive an injection of DCs at his/her assigned dose once every week during the first 6 week. The dose of DCs is defined as 8\~10×10\^6.
Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately, at the present time the majority of clinical trials were in phase I that illustrated the safety. The efficacy of DCs against glioblastoma is still lack of sufficient randomized phase II study. According to our previous phase I study, here we designed this clinical trial in a triple-blind randomized manner to validate the efficacy of DCs vaccination.
Recently，an exploratory randomized phase II clinical trial have been completed （Cancer immunology \&immunotheapy ，2018，1677，1677-1688 ； PubMed ID: 30159779）， 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1wild type (WT) TERTMT patients, DCV treatment significantly prolonged OS (p \< 0.01) and PFS (p = 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment.
In the present study, IDH1WTTERTMT subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy. However，It is noted that IDH1WTTERTMTGBM patients was analysed in a cohort samples which are not randomlized and the present study population is too small to evaluate conclusively demographic criteria for entry and patient recruitment. the results of the present study should be confirmed in a random cohort of IDH1WTTERTMT GBM patients. Accordingly , we made some modifications to the original plan, and are currently recruiting new participants.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: