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Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma (Combi G-Vax)

Primary Purpose

Glioblastoma, Vaccination

Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Autologous Dendritic Cells (DC) vaccine
Temozolomide
Sponsored by
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring glioblastoma, dendritic cells, vaccine, temozolomide, Stupp regimen, cellular therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

After signing the informed consent form for pre-screening, patient will assess the procedures to obtain sufficient leukapheretic material for the dendritic cell vaccine manufacturing and will perform the standard radiochemotherapy treatment (Stupp regimen) for the disease.

For the pre-screening phase of the study the eligibility criteria are:

  1. Histologically confirmed "monofocal" glioblastoma
  2. Near-complete resection (= 5 ml residual tumor volume) confirmed by "central neuroradiologist on magnetic resonance imaging (MRI) or CT scan within 72 h postoperative"
  3. Karnofsky performance status (KPS) = 70% or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix A)
  4. Be willing and able to provide written informed consent/assent for the pre-screening phase of the trial.
  5. Be = 18 years of age on day of signing informed consent.
  6. Life expectancy of greater than 12 weeks.
  7. Patient suitable for the collection of biological material from leukapheresis:

    serological tests HIV, hepatitis B virus (HBV), HCV, Treponema pallidum negative; normal cardiological parameters (ECG and cardiological examination); evaluation by transfusionist to exclude possible contraindications to leukapheresis.

  8. Patient candidate to standard radiochemotherapy (Stupp regimen)
  9. Appropriate 12-lead ECG and echocardiogram.

After pre-screening, patient will be enrolled based on subsequent Inclusion Criteria:

  1. Histologically confirmed "monofocal" glioblastoma
  2. The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) and must fulfil all the acceptance criteria prescribed by the Good Manufacturing Practices (GMP) procedures.
  3. Availability of sufficient leukapheretic material for the preparation of the vaccine product.
  4. No progressive disease near-complete resection (= 5 ml residual tumor volume) confirmed by MRI after standard radiochemotherapy treatment (Stupp regimen)
  5. Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments.
  6. Be willing and able to provide written informed consent/assent for the trial.
  7. Be >= 18 years of age on day of signing informed consent.
  8. Have a Karnofsky performance status (KPS) = 70% or a performance status of 0 or 1 on the ECOG Performance Scale.
  9. Demonstrate adequate organ and marrow function

Exclusion Criteria:

  1. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 10 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  2. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  3. Has a known history of active Bacillus Tuberculosis (TB)
  4. Previous treatment with a cancer vaccine
  5. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery.
  6. Any known history of or is positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous.
  7. Has received a live vaccine within 30 days of planned start of study therapy.

Sites / Locations

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental treatment

Arm Description

Induction phase: 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4). Maintenance phase: 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments. After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.

Outcomes

Primary Outcome Measures

clinical activity
Progression free survival (PFS), measured as the proportion of patients without progression of disease at three months from leukapheresis
Incidence of Treatment-Emergent Adverse Events
Proportion of patients experienced grade 3 or higher adverse events related to the study treatment

Secondary Outcome Measures

Immune response in vivo
Evaluation of the prognostic role of a positive DTH test after at least four vaccine administrations
Clinical Outcome (Overall Survival (OS))
Overall Survival (OS) is calculated as the time from the date of leukapheresis to the date of death for any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.
Immunological efficacy
Immunological efficacy: ability to enhance the proportion of circulating immune effectors specific for tumor antigens; evaluation of the persistence of an anti-tumor immune response; determination of plasma levels of a panel of inflammatory cytokines and pro-angiogenic factors; evaluation of the prognostic and predictive role of tumor antigen expression in tumor tissue; analysis of the prognostic and predictive role of immune cells in the peripheral blood and in the tumor microenvironment
Human leukocyte antigen (HLA) class I and II characterization characterization of patients
Explorative endpoint (optional participation for patients): HLA class I and II characterization of patients

Full Information

First Posted
August 19, 2020
Last Updated
February 15, 2023
Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
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1. Study Identification

Unique Protocol Identification Number
NCT04523688
Brief Title
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma
Acronym
Combi G-Vax
Official Title
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma: a Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 25, 2021 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen).
Detailed Description
Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen). The experimental treatment consists of an induction phase with 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4), followed by a maintenance phase consisting of 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments. After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject. Primary objectives are clinical activity and safety of the study treatment. Secondary objectives are the evaluation of the prognostic role of the positive Delayed-Type Hypersensitivity (DTH) skin test after at least four vaccine administrations, the OS and the immunological efficacy of the study treatment. A series of exploratory objectives will be also assessed on samples from patients who participate to this optional part of the trial. Simon's two-stage design (Simon, 1989) will be used for the sample size calculation. A planned interim analysis will be done after the recruitment of the first 9 evaluable patients for toxicity and for efficacy. If study will not be stopped due to lack of safety or efficacy, a total of 28 evaluable patients will be enrolled for the trial. Time to events (PFS and OS) will be calculated with the Kaplan-Meier method and the analysis was performed on the eligible population. For the primary objective, the proportion of patients without progression at three months from leukapheresis date will be evaluated. The proportion of patients experiencing vaccine-related grade ≥ 3 adverse events (AEs) during the treatment will be inferred by means of the two-sided Clopper-Pearson, or a more appropriate one, 95% confidence interval. Descriptive statistics will be used to assess the extent of the secondary endpoints.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Vaccination
Keywords
glioblastoma, dendritic cells, vaccine, temozolomide, Stupp regimen, cellular therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental treatment
Arm Type
Experimental
Arm Description
Induction phase: 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4). Maintenance phase: 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments. After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.
Intervention Type
Biological
Intervention Name(s)
Autologous Dendritic Cells (DC) vaccine
Intervention Description
10×10exp6 autologous dendritic cells loaded with autologous tumour homogenate given by intradermal injection (day 1)
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
Adjuvant temozolomide assumed orally from day 1 to 5 (start on week 5). Dosage: 150mg/m2/day for the first cycle and 200 mg/m2/day for subsequent cycles (q28).
Primary Outcome Measure Information:
Title
clinical activity
Description
Progression free survival (PFS), measured as the proportion of patients without progression of disease at three months from leukapheresis
Time Frame
about 55 months
Title
Incidence of Treatment-Emergent Adverse Events
Description
Proportion of patients experienced grade 3 or higher adverse events related to the study treatment
Time Frame
about 55 months
Secondary Outcome Measure Information:
Title
Immune response in vivo
Description
Evaluation of the prognostic role of a positive DTH test after at least four vaccine administrations
Time Frame
about 32 months
Title
Clinical Outcome (Overall Survival (OS))
Description
Overall Survival (OS) is calculated as the time from the date of leukapheresis to the date of death for any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.
Time Frame
about 55 months
Title
Immunological efficacy
Description
Immunological efficacy: ability to enhance the proportion of circulating immune effectors specific for tumor antigens; evaluation of the persistence of an anti-tumor immune response; determination of plasma levels of a panel of inflammatory cytokines and pro-angiogenic factors; evaluation of the prognostic and predictive role of tumor antigen expression in tumor tissue; analysis of the prognostic and predictive role of immune cells in the peripheral blood and in the tumor microenvironment
Time Frame
about 55 months
Title
Human leukocyte antigen (HLA) class I and II characterization characterization of patients
Description
Explorative endpoint (optional participation for patients): HLA class I and II characterization of patients
Time Frame
about 32 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
After signing the informed consent form for pre-screening, patient will assess the procedures to obtain sufficient leukapheretic material for the dendritic cell vaccine manufacturing and will perform the standard radiochemotherapy treatment (Stupp regimen) for the disease. For the pre-screening phase of the study the eligibility criteria are: Histologically confirmed "monofocal" glioblastoma Near-complete resection (= 5 ml residual tumor volume) confirmed by "central neuroradiologist on magnetic resonance imaging (MRI) or CT scan within 72 h postoperative" Karnofsky performance status (KPS) = 70% or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix A) Be willing and able to provide written informed consent/assent for the pre-screening phase of the trial. Be = 18 years of age on day of signing informed consent. Life expectancy of greater than 12 weeks. Patient suitable for the collection of biological material from leukapheresis: serological tests HIV, hepatitis B virus (HBV), HCV, Treponema pallidum negative; normal cardiological parameters (ECG and cardiological examination); evaluation by transfusionist to exclude possible contraindications to leukapheresis. Patient candidate to standard radiochemotherapy (Stupp regimen) Appropriate 12-lead ECG and echocardiogram. After pre-screening, patient will be enrolled based on subsequent Inclusion Criteria: Histologically confirmed "monofocal" glioblastoma The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) and must fulfil all the acceptance criteria prescribed by the Good Manufacturing Practices (GMP) procedures. Availability of sufficient leukapheretic material for the preparation of the vaccine product. No progressive disease near-complete resection (= 5 ml residual tumor volume) confirmed by MRI after standard radiochemotherapy treatment (Stupp regimen) Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments. Be willing and able to provide written informed consent/assent for the trial. Be >= 18 years of age on day of signing informed consent. Have a Karnofsky performance status (KPS) = 70% or a performance status of 0 or 1 on the ECOG Performance Scale. Demonstrate adequate organ and marrow function Exclusion Criteria: Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 10 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has a known history of active Bacillus Tuberculosis (TB) Previous treatment with a cancer vaccine Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery. Any known history of or is positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous. Has received a live vaccine within 30 days of planned start of study therapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Oriana Nanni, DR
Phone
+390543739266
Email
oriana.nanni@irst.emr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Miserocchi, DR
Email
cc.ubsc@irst.emr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Ridolfi, DR
Organizational Affiliation
IRST IRCCS
Official's Role
Study Chair
Facility Information:
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Ridolfi, DR
Phone
+390543 739274
Email
laura.ridolfi@irst.emr.it

12. IPD Sharing Statement

Learn more about this trial

Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma

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