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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:
NCT01006044
First received: October 30, 2009
Last updated: September 2, 2014
Last verified: September 2014
  Purpose
  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.

Condition Intervention Phase
Glioblastoma Multiforme
Biological: autologous dendritic cells
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Clinica Universidad de Navarra, Universidad de Navarra:

Primary Outcome Measures:
  • Evaluation of the treatment impact on progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety evaluation [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    1. Direct effects attributable cell obtaining and administration
    2. Adverse events during treatment
    3. Neurological deterioration quantified using the NIH Stroke Scale
    4. Autoimmune phenomena

  • Evaluation of impact on other efficiency clinical parameters [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    1. Overall survival
    2. Quality of life measured with EORTC questionnaire

  • Study of specific immune response and correlates with clinical outcome [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    1. Delayed hypersensitivity
    2. Humoral response to autologous tumor cells/tumoral lysate
    3. Cellular response (proliferation, cytokine production, specific cytotoxicity)

  • Cell line characterization and correlate the final product with clinical efficacy [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    a. Phenotypic studies


Enrollment: 26
Study Start Date: October 2009
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccination
Autologous Dendritic cells loaded with tumor lysate
Biological: autologous dendritic cells
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006044

Locations
Spain
Clínica Universidad de Navarra
Pamplona, Spain, 31008
Sponsors and Collaborators
Clinica Universidad de Navarra, Universidad de Navarra
Investigators
Study Director: Felipe Prosper, MD, PhD Clinica Universidad de Navarra
  More Information

Publications:
Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier: NCT01006044     History of Changes
Other Study ID Numbers: DEND/GM, 2009-009879-35
Study First Received: October 30, 2009
Last Updated: September 2, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:
Glioblastoma multiforme, vaccine, dendritic cells, glioma

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 30, 2014