Efficacy & Safety of Autologous Dendritic Cell Vaccination in Glioblastoma Multiforme After Complete Surgical Resection

Prospective, Phase II Clinical Trial to Evaluate Efficacy and Safety of Autologous Dendritic Cell Vaccination in Glioblastoma Multiforme Patients After Complete Surgical Resection With Fluorescence Microscope

1. Primary outcome measure:

   a.Evaluation of the treatment impact on progression-free survival.

2. Secondary outcome measures:

   1. Safety evaluation.

      • Direct effects attributable cell obtaining and administration.
      • Adverse events during treatment.
      • Neurological deterioration quantified using the NIH Stroke Scale.
      • Autoimmune phenomena.

   2. Evaluation of impact on other efficiency clinical parameters.

      • Overall survival.
      • Quality of life measured with EORTC questionnaire.

   3. Study of specific immune response and correlates with clinical outcome.

      • Delayed hypersensitivity.
      • Humoral response to autologous tumor cells/tumoral lysate.
      • Cellular response (proliferation, cytokine production, specific cytotoxicity).

   4. Cell line characterization and correlate the final product with clinical efficacy.

      • Phenotypic studies.

A prospective, open-label, unicentric phase II trial, historical control and non-randomized.

The study will try to evaluate the efficiency and safety of the experimental treatment using a cell therapy product (tumor lysate-pulsed autologous dendritic cell vaccine) in patients with glioblastoma multiforme in whom a gross total resection is feasible. Patients will receive standard first-line therapy (surgery before radio-chemotherapy) along with the experimental treatment. The experimental treatment consists in subcutaneous vaccination with a suspension of autologous dendritic cells (cells from the same patient) produced by cell culture from monocytes from the same patient extracted by leukapheresis and pulsed with a lysate of the patient´s tumoral tissue. The first four vaccines will be administered on a monthly basis, concomitantly with the standard chemo and radiotherapy treatments, the next four vaccines, every other month and the four last vaccinations every three months.The results obtained will be compared with those of an historical control study, where patients received a standard treatment without the experimental vaccine.

Inclusion Criteria:

• Patients with histological diagnosis of glioblastoma that have not received any previous chemotherapy or radiotherapy treatment.
• Patients are able to give informed consent and willing to comply with the protocol requirements during the study period.
• Age between 18 and 70 years
• Negative pregnancy test In female fertile subjects
• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Complete/Total resection of tumour with surgery guided by fluorescence microscopy and 5-aminolevulinic acid, observed with post operative magnetic resonance imaging. The residual lesion must be null or ≤ 1 cm3 by contrast capturing.
• Enough tumor tissue available for the cellular vaccine elaboration

Exclusion Criteria:

• Patients with infections, severe diseases or hepatic, renal or medullary failures, that in the investigator's opinion, are not eligible to participate in the study.
• Participation in other clinical trial. If the patient has participated in other clinical trial within previous months, the patient has to complete the washout period required by de the investigator.
• Patients with diagnosis of other neoplasia, except basal cell or squamous cell skin, carcinoma in situ of the cervix properly treated or other tumour curatively treated and no evidence of relapse for at least 3 years. Those cases with coexisting tumours of long-term survival prediction will be considered individually.
• Pregnant or breast-feeding women.
• Patients who need immunosuppressive drugs.
• Positive serology for HIV , hepatitis B (HBsAg) or hepatitis C virus.
• Impossible to get enough material for at least 6 cellular vaccine production.
• Absolute contraindication for the patient to receive other steps of standard treatment of glioblastoma (surgery, radio and chemotherapy)