Back to resultsA Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma (DENDR-STEM)
Primary Purpose
de Novo Glioblastoma
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
GSC-loaded autologous dendritic cells
Sponsored by
About this trial
This is an interventional treatment trial for de Novo Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 and ≤70 years;
- Histological diagnosis of de novo GBM (i.e. not secondary GBM);
- Gross total resection as evaluated by MRI performed within 72 hours from surgery;
- Karnofsky Performance Status (KPS) ≥60 at the time of first progression;
- Written informed consent.
Exclusion Criteria:
- Pregnancy or breast feeding;
- Participation in other clinical trials with experimental drugs simultaneously;
- Mandatory treatment with corticosteroids or salicylates in anti-inflammatory dose;
- Presence of sub-ependymal diffusion of the tumor;
- Presence of multi-focal GBM lesion;
- Haematology: leukocytes (WBC) < 3x103/μl, absolute lymphocyte count< 0.5x103/μl, Absolute neutrophil count (ANC) < 1x103/μl, hemoglobin< 9 g/dL, platelets< 50x103/μl within two days prior to leukapheresis;
- AST (SGOT)/ALT (SGPT) ≥3 X institutional Upper Limit Normal (ULN) at the time of leukapheresis;
- Serum creatinine>1.5 ULN or calculated creatinine clearance < 60 ml/min at time of surgery;
- Documented immune deficiency;
- Documented systemic autoimmune disease;
- Positivity for HBV, HIV, HCV, Treponema Pallidum;
- Allergies to any component of the DC vaccine;
- Other active malignancy.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSC-loaded autologous dendritic cells
Arm Description
DC-GSC immunotherapy. Six vaccinations are envisaged. The first three vaccinations will be performed every two weeks; subsequent three vaccinations every month. The first vaccination will be performed using 20 million DC, the second and third with 10 million DC; and from the 4th vaccine 5 million DC
Outcomes
Primary Outcome Measures
Safety: - incidence, nature, severity and seriousness of AEs, according to NCI-CTCAE version 4.0; - maximum toxicity grade and percentage of patients experiencing grade 3-4 by each patient for each specific toxicity; - patients with at least a SAE.
Safety will be assessed as follows:
Incidence, nature, severity and seriousness of AEs, according to NCI-CTCAE, version 4.0
Maximum toxicity grade experienced by each patient for each specific toxicity
Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
Patients with at least a SAE
Patients with at least a SADR
Patients with at least a Suspected Unexpected Serious Associated Reaction (SUSAR).
Incidence, severity and type of AEs throughout the study, and toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria for AE (CTCAE), version 4.0
Secondary Outcome Measures
Probability to obtain the full vaccine dosage, i.e. the percentage of patients who will be treated with at least 2 vaccine injections.
Immunologic activity
activity of immunotherapy in terms of its effect on immune response of predefined immune effector cells.
Progression free survival (PFS)
Progression Free Survival after immunotherapy is defined for each patient as the time of onset of immunotherapy to the date of second progression.
Quality of life
Treatment effect on quality of life will be assessed using the EORTC QLQ-C30 and BN-20.
Quality of life
Treatment effect on quality of life will be assessed using the BN-20 questionnaire.
Overall survival (OS)
Overall Survival after immunotherapy is defined for each patient as the time of onset of immunotherapy to the date of death from any cause.
Full Information
NCT ID
NCT02820584
First Posted
February 22, 2016
Last Updated
September 10, 2019
Sponsor
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
1. Study Identification
Unique Protocol Identification Number
NCT02820584
Brief Title
A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma
Acronym
DENDR-STEM
Official Title
A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Mono-center, un-controlled, open label, first in human, clinical trial. Approximately 20 patients (in order to achieve 12 valuable patients). The expected accrual time would range between 12 and 18 months. Follow-up, including clinical, immune and radiological monitoring will end two years after the initial surgery of the last patient enrolled. The primary objective will be to assess the activity of immunotherapy in terms of its effect on immune response. In particular we will investigate the effect of treatment on effector cells including CD8 T cells, NK cells and Natural Killer T (NKT) cells. The sample size of 12 eligible patients was identified on ethical and practical considerations, rather than by a formal sample size calculation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
de Novo Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSC-loaded autologous dendritic cells
Arm Type
Experimental
Arm Description
DC-GSC immunotherapy. Six vaccinations are envisaged. The first three vaccinations will be performed every two weeks; subsequent three vaccinations every month. The first vaccination will be performed using 20 million DC, the second and third with 10 million DC; and from the 4th vaccine 5 million DC
Intervention Type
Biological
Intervention Name(s)
GSC-loaded autologous dendritic cells
Primary Outcome Measure Information:
Title
Safety: - incidence, nature, severity and seriousness of AEs, according to NCI-CTCAE version 4.0; - maximum toxicity grade and percentage of patients experiencing grade 3-4 by each patient for each specific toxicity; - patients with at least a SAE.
Description
Safety will be assessed as follows:
Incidence, nature, severity and seriousness of AEs, according to NCI-CTCAE, version 4.0
Maximum toxicity grade experienced by each patient for each specific toxicity
Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
Patients with at least a SAE
Patients with at least a SADR
Patients with at least a Suspected Unexpected Serious Associated Reaction (SUSAR).
Time Frame
18 months
Title
Incidence, severity and type of AEs throughout the study, and toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria for AE (CTCAE), version 4.0
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Probability to obtain the full vaccine dosage, i.e. the percentage of patients who will be treated with at least 2 vaccine injections.
Time Frame
18 months
Title
Immunologic activity
Description
activity of immunotherapy in terms of its effect on immune response of predefined immune effector cells.
Time Frame
18 months
Title
Progression free survival (PFS)
Description
Progression Free Survival after immunotherapy is defined for each patient as the time of onset of immunotherapy to the date of second progression.
Time Frame
18 months
Title
Quality of life
Description
Treatment effect on quality of life will be assessed using the EORTC QLQ-C30 and BN-20.
Time Frame
18 months
Title
Quality of life
Description
Treatment effect on quality of life will be assessed using the BN-20 questionnaire.
Time Frame
18 months
Title
Overall survival (OS)
Description
Overall Survival after immunotherapy is defined for each patient as the time of onset of immunotherapy to the date of death from any cause.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 and ≤70 years;
Histological diagnosis of de novo GBM (i.e. not secondary GBM);
Gross total resection as evaluated by MRI performed within 72 hours from surgery;
Karnofsky Performance Status (KPS) ≥60 at the time of first progression;
Written informed consent.
Exclusion Criteria:
Pregnancy or breast feeding;
Participation in other clinical trials with experimental drugs simultaneously;
Mandatory treatment with corticosteroids or salicylates in anti-inflammatory dose;
Presence of sub-ependymal diffusion of the tumor;
Presence of multi-focal GBM lesion;
Haematology: leukocytes (WBC) < 3x103/μl, absolute lymphocyte count< 0.5x103/μl, Absolute neutrophil count (ANC) < 1x103/μl, hemoglobin< 9 g/dL, platelets< 50x103/μl within two days prior to leukapheresis;
AST (SGOT)/ALT (SGPT) ≥3 X institutional Upper Limit Normal (ULN) at the time of leukapheresis;
Serum creatinine>1.5 ULN or calculated creatinine clearance < 60 ml/min at time of surgery;
Documented immune deficiency;
Documented systemic autoimmune disease;
Positivity for HBV, HIV, HCV, Treponema Pallidum;
Allergies to any component of the DC vaccine;
Other active malignancy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gaetano Finocchiaro, MD
Organizational Affiliation
Fondazione IRCCS Istituto Neurologico "Carlo Besta" di Milano
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma
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