Clinical trial NCT02820584: A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma
Official title: A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: de Novo Glioblastoma
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Sponsor class: OTHER
First posted: 2016-07-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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.
timeFrame: 18 months
measure: 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
timeFrame: 18 months
Secondary outcomes:
measure: Probability to obtain the full vaccine dosage, i.e. the percentage of patients who will be treated with at least 2 vaccine injections.
timeFrame: 18 months
measure: Immunologic activity
timeFrame: 18 months
measure: Progression free survival (PFS)
timeFrame: 18 months
measure: Quality of life
timeFrame: 18 months
measure: Quality of life
timeFrame: 18 months
measure: Overall survival (OS)
timeFrame: 18 months
Other outcomes:
Locations:
Study officials:
affiliation: Fondazione IRCCS Istituto Neurologico "Carlo Besta" di Milano
name: Gaetano Finocchiaro, MD
role: PRINCIPAL_INVESTIGATOR
References: