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

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

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.

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.