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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study of Immunotherapy With GSC -Loaded Dendritic Cells in Patients With Recurrent Glioblastoma

Conditions
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de Novo Glioblastoma

Intervention / Treatment
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* Biological: GSC-loaded autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSC-loaded autologous dendritic cells<br>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<br> <br> |

What is the study measuring?
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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 |