Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    gliovax | glioblastoma
Previous Study | Return to List | Next Study

Efficiency of Vaccination With Lysate-loaded Dendritic Cells in Patients With Newly Diagnosed Glioblastoma (GlioVax)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03395587
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : May 20, 2019
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

Brief Summary:
The primary objective of the study is to determine whether overall survival of newly diagnosed glioblastoma patients treated with lysate-loaded, mature dendritic cell vaccines as add-on to the standard of care consisting of resection, radiotherapy with concomitant temozolomide chemotherapy and subsequent adjuvant temozolomide chemotherapy is superior to the treatment with the standard of care alone.

Condition or disease Intervention/treatment Phase
Glioblastoma Biological: Autologous, tumor lysate-loaded, mature dendritic cells (DC) Drug: standard therapy Phase 2

Detailed Description:
This is a multicenter, randomized, phase 2 study, integrating vaccination with tumorlysate-loaded mature dendritic cells into standard radio/temozolomide-chemotherapy of newly diagnosed glioblastoma patients with near-complete resection after fluorescence-guided resection. Only patients with confirmed gross-total resection and a residual tumor volume below 5 ml will be eligible for the trial. Vaccination will be performed after radio- and concomitant temozolomide chemotherapy and during the first three cycles of adjuvant TMZ.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: prospective, multicenter, open-label, randomized phase 2 study with two parallel groups
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Vaccination With Lysate-loaded, Mature Dendritic Cells Integrated Into Standard Radiochemotherapy in Newly Diagnosed Glioblastoma
Actual Study Start Date : March 6, 2018
Estimated Primary Completion Date : September 6, 2022
Estimated Study Completion Date : June 6, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental intervention
Fluorescence-guided surgery (day 0) Leukapheresis (wk4) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) vaccination with autologous, tumor lysate-loaded, mature dendritic cells (DC) (7x, 2 - 10 x 106 DC each, intradermal injection, weekly wk11-14, wk17, 21, 25)Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)
Biological: Autologous, tumor lysate-loaded, mature dendritic cells (DC)
Advanced therapy medicinal product (ATMP) produced at the University Hospital Düsseldorf according to Good Manufacturing Practice (GMP) with production permission according §13 AMG (German Drug Law) of the local authorities (Bezirks¬regierung Düsseldorf)
Other Name: dendritic cell vaccination

Control intervention

Standard therapy:

Fluorescence-guided surgery (day 0) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)

Drug: standard therapy
temozolomide, fractionated radiochemotherapy
Other Name: temozolomide, fractionated radiochemotherapy




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Day of surgery until death of any cause assessed up to 34 months ]
    Overall survival as measured from the day of surgery until death from any cause assessed up to 34 months


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Day of surgery until day of diagnosis of tumor progression assessed upto 34 months ]
    Progression-free survival as measured from the day of surgery until diagnosis of tumor progression by MRI scan according to modified Response Assessment in Neuro-Oncology (RANO) criteria assessed up to 34 months

  2. OS rates [ Time Frame: 6, 12 and 24 months after the day of surgery ]
    OS rates at 6, 12 and 24 months after the day of surgery

  3. PFS rates [ Time Frame: 6, 12 and 24 months after the day of surgery ]
    PFS rates at 6, 12 and 24 months after the day of surgery

  4. Frequency and severity of adverse events [ Time Frame: 34 months ]
    Safety based on the frequency and severity of adverse events (AE) with toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 4.03 (CTCAE 4.03)

  5. Karnofsky Performance Status [ Time Frame: 34 months ]
    Overall and neurological performance based on the Karnofsky performance status (MMSE-2)

  6. MMSE-2 [ Time Frame: 34 months ]
    Overall and neurological performance based on the Minimal Mental State Examination 2 (MMSE-2)

  7. Quality of life of cancer patients [ Time Frame: 34 months ]
    Quality of life as determined by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 3.0

  8. Quality of life in patients with brain cancer [ Time Frame: 34 months ]
    Quality of life as determined by the European Organization for Research and Treatment of Cancer (EORTC) Brain Cancer Module QLQ-BN20

  9. Psychological distress in oncology patients [ Time Frame: 34 months ]
    Quality of life as determined by the Distress Thermometer (DT)

  10. Psychological distress, anxiety and depression [ Time Frame: 34months ]
    Quality of life as determined by the Hospital Anxiety and Depression Scale (HADS) for psycho-oncological strain assessment



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Determined at pre-screening (prior to surgery; wk-3 - wk-1):

  • Patients ≥ 18 years of age at surgery.
  • Patients must be in a cognitive state to understand and sign the informed consent indicating that they are aware of the investigational nature and procedures of the study.
  • First written informed consent for screening for eligibility, including tumor tissue collection, transfer and processing, central neuropathological evaluation of Tumor sample, central neuroradiological assessment of extent of resection, infectious disease (HIV, HBV, HCV, Treponema pallidum) testing, determination of MGMT promoter methylation status and pregnancy testing.

Determined at screening (at and post-surgery; d0 - wk3):

  • Newly diagnosed, monofocal GBM, IDH wildtype (WHO grade IV), including the histological variants of gliosarcoma and giant cell glioblastoma, confirmed by central neuropathologist according to the WHO classification of central nervous System tumors 2016. Tumors may cross into, but not beyond the corpus callosum.
  • Near-complete resection (≤ 5 ml residual contrast enhancing tumor volume) confirmed by central neuroradiologist on MRI scan within 72 h postoperative; awake surgery and second look surgery are possible, if medically indicated.
  • Sterile tumor sample of ≥ 150 mg with tumor cell frequency ≥ 60% as determined by central neuropathologist available for vaccine production.
  • Successful production of sterile, avital tumor lysate.
  • Karnofsky performance status ≥ 70%.
  • Adequate hepatic (serum glutamate pyruvate transferase/alanine transaminase (SGPT/ALT), serum glutamic oxaloacetate transaminase/aspartate transaminase (SGOT/AST) and alkaline phosphatase ≤ 3-times upper limit of normal (ULN); bilirubin ≤ 1.5-times ULN) and renal functions (creatinine ≤ 1.5-times ULN).
  • Adequate bone marrow function (hemoglobin ≥ 10 g/dl, thrombocytes ≥ 100,000/μl, white blood cell count ≥ 3,000/μl; neutrophil count ≥ 1,500/μl).
  • Prothrombin time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x ULN unless therapeutically warranted. International normalized ratio (INR) (in absence of anticoagulation treatment) ≤ 1.5.
  • Systemic corticosteroids tapered down to ≤ 2 mg of dexamethasone or equivalent per day within 7 days postoperative (use of corticosteroids during the treatment period should be avoided, however it is possible if clinically indicated, but may require interruption of dendritic cell vaccination).
  • Female patients with reproductive potential and male generative patients and their female partners must agree to be true abstinent or to use a highly effective form of contraception (pearl index < 1%) during the trial.
  • Patients must be in a cognitive state to understand and sign the informed consent indicating that they are aware of the investigational nature and procedures of the study.
  • Written informed consent to participate in study.

Exclusion Criteria:

determined at pre-screening (prior to surgery; wk-3 - wk-1):

  • Medical history of severe acute or chronic disease with poor prognosis, e.g. severe coronary heart disease, heart failure (New York Heart Association classes III/IV), severe poorly controlled diabetes, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
  • Medical history of severe autoimmune disorder or immunodeficiency or patients with organ allograft.
  • Medical history of bleeding diathesis or coagulopathy.
  • Prior malignancy during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with prostate-specific antigen (PSA) level less than ULN.
  • Previous radiotherapy to head and neck.
  • Known allergy or intolerability to TMZ, dacarbazine, the contrast agent or to components of the dendritic cell vaccine.
  • Current treatment of glioblastoma in another clinical trial with therapeutic intervention or current use of any other investigational agent.
  • Known pregnancy or breast feeding.
  • No known severe infection requiring treatment.
  • Accommodation in an institution due to legal orders (§40(4) AMG).
  • Evidence of current drug or alcohol abuse. determined at screening (at and post-surgery; d0 - wk3):
  • Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum or other severe infection requiring treatment.
  • Accommodation in an institution due to legal orders (§40(4) AMG).
  • Pregnant or breast feeding female patients. From pre-menopausal female patients with childbearing potential a negative pregnancy test must be obtained.
  • Any psycho-social condition hampering compliance with the study protocol.
  • MGMT promoter methylation status equivocal.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03395587


Contacts
Layout table for location contacts
Contact: Michael Sabel, Prof. MD +49 211 8116276 Michael.Sabel@med.uni-duesseldorf.de
Contact: Marion Rapp, PD MD +49 211 8107458 Marion.Rapp@med.uni-duesseldorf.de

Locations
Layout table for location information
Germany
Klinik für Neurologie, Knappschaftskrankenhaus Bochum Recruiting
Bochum, Northrhine Westphalia, Germany, 44829
Contact: Uwe Schlegel, Prof. MD    00492342993719    neurologie@kk-bochum.de   
Contact: Rekowski Sylvia    00492342993719    sylvia.rekowski@kk-bochum.de   
Sub-Investigator: Thomas Kowalski         
Principal Investigator: Uwe Schlegel, Prof. MD         
Klinik für Neurochirurgie, Sana Kliniken Duisburg Recruiting
Duisburg, Northrhine Westphalia, Germany, 47055
Contact: Jung Su Zin, Dr. med.    00492037332401    suzin.jung@sana.de   
Principal Investigator: Catharina Junghans, Dr. med.         
Sub-Investigator: Jung Su Zin, Dr. med.         
Neurochirurgische Klinik, Universitätsklinikum Düsseldorf Recruiting
Düsseldorf, Northrhine Westphalia, Germany, 40225
Contact: Michael C. Sabel, Prof. MD    00492118116276    michael.sabel@med.uni-duesseldorf.de   
Contact: Natalie Sevens    00492118117881      
Sub-Investigator: Marion Rapp, PD MD         
Principal Investigator: Michael Sabel, Prof. MD         
Klinik für Allgemeine Neurologie, Universitätsklinikum Münster Recruiting
Münster, Northrhine Westphalia, Germany, 48149
Contact: Oliver Grauer, PD Dr. med.    0492518346814    oliver.grauer@ukmuenster.de   
Principal Investigator: Oliver Grauer, PD Dr. med.         
Sub-Investigator: Ole Simon, Dr. med.         
Helios Klinikum Krefeld, Klinik für Neurochirurgie Recruiting
Krefeld, Germany, 47805
Contact: Michael Stoffel, Prof. MD    +492151321320    Michael.Stoffel@helios-gesundheit.de   
Principal Investigator: Michael Stoffel, Prof. MD         
Sub-Investigator: Knut Send, MD         
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
German Federal Ministry of Education and Research
Investigators
Layout table for investigator information
Principal Investigator: Michael Sabel, Prof. MD Department of Neurosurgery

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT03395587     History of Changes
Other Study ID Numbers: GlioVax
First Posted: January 10, 2018    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Heinrich-Heine University, Duesseldorf:
glioblastoma,
immunotherapy
dendritic cells
vaccination
Additional relevant MeSH terms:
Layout table for 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
Temozolomide
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents