A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma (DENDR-STEM)

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.

Study Overview

• Status: Completed
• Conditions: de Novo Glioblastoma
• Intervention / Treatment: Biological: GSC-loaded autologous dendritic cells

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GSC-loaded autologous dendritic cells; 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	Biological: GSC-loaded autologous dendritic cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	18 months
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		18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability to obtain the full vaccine dosage, i.e. the percentage of patients who will be treated with at least 2 vaccine injections.		18 months
Immunologic activity	activity of immunotherapy in terms of its effect on immune response of predefined immune effector cells.	18 months
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.	18 months
Quality of life	Treatment effect on quality of life will be assessed using the EORTC QLQ-C30 and BN-20.	18 months
Quality of life	Treatment effect on quality of life will be assessed using the BN-20 questionnaire.	18 months
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.	18 months

Collaborators and Investigators

• Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
• Investigators: Principal Investigator: Gaetano Finocchiaro, MD, Fondazione IRCCS Istituto Neurologico "Carlo Besta" di Milano

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): June 1, 2017
• Study Completion (ACTUAL): June 1, 2017

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (ESTIMATE): July 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: DENDR-STEM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO