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

Primary Purpose

Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
autologous dendritic cells
Sponsored by
Clinica Universidad de Navarra, Universidad de Navarra
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma multiforme, vaccine, dendritic cells, glioma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Clínica Universidad de Navarra

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccination

Arm Description

Autologous Dendritic cells loaded with tumor lysate

Outcomes

Primary Outcome Measures

Evaluation of the treatment impact on progression-free survival

Secondary Outcome Measures

Safety evaluation
Direct effects attributable cell obtaining and administration Adverse events during treatment Neurological deterioration quantified using the NIH Stroke Scale Autoimmune phenomena
Evaluation of impact on other efficiency clinical parameters
Overall survival Quality of life measured with EORTC questionnaire
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)
Cell line characterization and correlate the final product with clinical efficacy
a. Phenotypic studies

Full Information

First Posted
October 30, 2009
Last Updated
September 2, 2014
Sponsor
Clinica Universidad de Navarra, Universidad de Navarra
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1. Study Identification

Unique Protocol Identification Number
NCT01006044
Brief Title
Efficacy & Safety of Autologous Dendritic Cell Vaccination in Glioblastoma Multiforme After Complete Surgical Resection
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clinica Universidad de Navarra, Universidad de Navarra

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary outcome measure: a.Evaluation of the treatment impact on progression-free survival. Secondary outcome measures: Safety evaluation. Direct effects attributable cell obtaining and administration. Adverse events during treatment. Neurological deterioration quantified using the NIH Stroke Scale. Autoimmune phenomena. Evaluation of impact on other efficiency clinical parameters. Overall survival. Quality of life measured with EORTC questionnaire. 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). Cell line characterization and correlate the final product with clinical efficacy. Phenotypic studies.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
Keywords
Glioblastoma multiforme, vaccine, dendritic cells, glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vaccination
Arm Type
Experimental
Arm Description
Autologous Dendritic cells loaded with tumor lysate
Intervention Type
Biological
Intervention Name(s)
autologous dendritic cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Evaluation of the treatment impact on progression-free survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Safety evaluation
Description
Direct effects attributable cell obtaining and administration Adverse events during treatment Neurological deterioration quantified using the NIH Stroke Scale Autoimmune phenomena
Time Frame
5 years
Title
Evaluation of impact on other efficiency clinical parameters
Description
Overall survival Quality of life measured with EORTC questionnaire
Time Frame
5 years
Title
Study of specific immune response and correlates with clinical outcome
Description
Delayed hypersensitivity Humoral response to autologous tumor cells/tumoral lysate Cellular response (proliferation, cytokine production, specific cytotoxicity)
Time Frame
5 years
Title
Cell line characterization and correlate the final product with clinical efficacy
Description
a. Phenotypic studies
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felipe Prosper, MD, PhD
Organizational Affiliation
Clinica Universidad de Navarra
Official's Role
Study Director
Facility Information:
Facility Name
Clínica Universidad de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
10350260
Citation
Liau LM, Black KL, Prins RM, Sykes SN, DiPatre PL, Cloughesy TF, Becker DP, Bronstein JM. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999 Jun;90(6):1115-24. doi: 10.3171/jns.1999.90.6.1115.
Results Reference
background
PubMed Identifier
15758009
Citation
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
Results Reference
background
PubMed Identifier
17620423
Citation
Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Mol Cancer Ther. 2007 Jul;6(7):1909-19. doi: 10.1158/1535-7163.MCT-07-0047.
Results Reference
background
PubMed Identifier
28499389
Citation
Inoges S, Tejada S, de Cerio AL, Gallego Perez-Larraya J, Espinos J, Idoate MA, Dominguez PD, de Eulate RG, Aristu J, Bendandi M, Pastor F, Alonso M, Andreu E, Cardoso FP, Valle RD. A phase II trial of autologous dendritic cell vaccination and radiochemotherapy following fluorescence-guided surgery in newly diagnosed glioblastoma patients. J Transl Med. 2017 May 12;15(1):104. doi: 10.1186/s12967-017-1202-z.
Results Reference
derived

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

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