Ignite Creation Date:
2024-05-06 @ 1:22 PM
Last Modification Date:
2024-10-26 @ 1:13 PM
Study NCT ID:
NCT04002804
Status:
TERMINATED
Last Update Posted:
2019-07-01
First Post:
2019-06-10
Brief Title:
Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Recurrence Of Glioblastoma Multiforme
Sponsor:
Fondazione IRCCS Istituto Neurologico Carlo Besta
Organization:
Fondazione IRCCS Istituto Neurologico Carlo Besta
Study Overview
Official Title:
Phase I Clinical Trial Of Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Recurrence Of Glioblastoma Multiforme
Status:
TERMINATED
Status Verified Date:
2019-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Temozolomide does not favour immune response secondary GBM to be excluded
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Dendr2
Brief Summary:
Rationale of the Study Treatment for GBM currently consists of surgical resection of the tumour mass followed by radio- and chemotherapy Nonetheless overall prognosis still remains bleak recurrence is universal and recurrent GBM patients clearly need innovative therapies Dendritic cells DC immunotherapy could represent a well-tolerated long-term tumour-specific treatment to kill all residual tumour cells which infiltrate in the adjacent areas of the brain Preclinical investigations for the development of therapeutic vaccines against high grade gliomas based on the use of DC loaded with a mixture of glioma-derived tumor have been carried out in rat as well as in mouse models showing the capacity to generate a glioma-specific immune response Mature DC loaded with autologous tumor lysate have been used also for the treatment of patients with recurrent malignant brain tumors no major adverse events have been registered
Results about the use of immunotherapy for GBM patients are encouraging but further studies are necessary to find out the most effective and safe combination of immunotherapy with radio- and chemotherapy after exeresis of the tumour mass
Aim of the study Primary objective of the study is to evaluate treatment tolerability and to get preliminary information about efficacy Secondary objective is to evaluate the treatment effect on the immune response Additional objective is to identify a possible correlation between methylation status of the MGMT promoter and tumor response to treatment
A two-stage Simon design will be considered for the study The primary objectives of the study include the evaluation of a PFS6 rate in treated patients Assuming as outcome measure the percentage of PFS6 patients and of clinical interest an increase to 35 P1 of the historical control response rate of 20 P0 the null hypothesis will be rejected a005 b02 at the end of the first stage if the response rate will be 522 treated patients Fishers exact test In the second stage patients will be enrolled up to 72 overall The study will be successful if at least 19 subjects out of 72 have PFS6 months after the beginning of the treatment
Results about the use of immunotherapy for GBM patients are encouraging but further studies are necessary to find out the most effective and safe combination of immunotherapy with radio- and chemotherapy after exeresis of the tumour mass
Aim of the study Primary objective of the study is to evaluate treatment tolerability and to get preliminary information about efficacy Secondary objective is to evaluate the treatment effect on the immune response Additional objective is to identify a possible correlation between methylation status of the MGMT promoter and tumor response to treatment
A two-stage Simon design will be considered for the study The primary objectives of the study include the evaluation of a PFS6 rate in treated patients Assuming as outcome measure the percentage of PFS6 patients and of clinical interest an increase to 35 P1 of the historical control response rate of 20 P0 the null hypothesis will be rejected a005 b02 at the end of the first stage if the response rate will be 522 treated patients Fishers exact test In the second stage patients will be enrolled up to 72 overall The study will be successful if at least 19 subjects out of 72 have PFS6 months after the beginning of the treatment
Detailed Description:
Study Design Phase I 2-stage Simon design Simon et al 1997 single-centre un-controlled open label non randomized study
The therapeutic program will include radical surgical resection of the tumor followed by immunotherapy Immunotherapy will comprise 4 biweekly vaccinations first injections I II III IV 2 further monthly vaccinations injections V VI and a final vaccination injection VII 2 months after the sixth one
Injections I V VI and VII will contain 10 million tumor lysate-loaded DC while the others will be of 5 million cells only In correspondence to the third vaccine injection week 7 6 cycles of maintenance TMZ mTMZ will start On the basis of the patient clinical status further vaccine boosts will be considered as appropriate addition at the standard vaccination cycle
Study Population The first stage of the study will include 22 patients with recurrent GBM The overall population at the end of the study will consist of 72 patients
The therapeutic program will include radical surgical resection of the tumor followed by immunotherapy Immunotherapy will comprise 4 biweekly vaccinations first injections I II III IV 2 further monthly vaccinations injections V VI and a final vaccination injection VII 2 months after the sixth one
Injections I V VI and VII will contain 10 million tumor lysate-loaded DC while the others will be of 5 million cells only In correspondence to the third vaccine injection week 7 6 cycles of maintenance TMZ mTMZ will start On the basis of the patient clinical status further vaccine boosts will be considered as appropriate addition at the standard vaccination cycle
Study Population The first stage of the study will include 22 patients with recurrent GBM The overall population at the end of the study will consist of 72 patients
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