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Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)

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ClinicalTrials.gov Identifier: NCT03548571
Recruitment Status : Recruiting
First Posted : June 7, 2018
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Einar Vik-Mo, Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE April 30, 2018
First Posted Date  ICMJE June 7, 2018
Last Update Posted Date October 22, 2019
Actual Study Start Date  ICMJE April 26, 2018
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2018)
Progression free survival [ Time Frame: 2 years ]
Defined as time from first surgery to first certain progress of contrast enhancing tumor or clinical progression, according to the Response Assessment in Neuro-Oncology (RANO) criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03548571 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2018)
  • Overall survival [ Time Frame: 2 years from inclusion ]
    Survival from the time of diagnosis.
  • Patient reported quality of life, overall [ Time Frame: 2 years from inclusion ]
    Evaluated by EORTC Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse.
  • Patient reported quality of life, brain specific [ Time Frame: 2 years from inclusion ]
    Evaluated by EORTC Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse. It should always be complemented by the QLQ-C30.
  • Immunological response, skin [ Time Frame: 2 years from inclusion ]
    Evaluated by delayed type hypersensitivity reaction in skin.
  • Immunological response, cellular [ Time Frame: 2 years from inclusion ]
    Evaluated by lymphocyte clonal analysis.
  • Adverse events [ Time Frame: 2 years from inclusion ]
    Classified according to Common Terminology Criteria for Adverse Events (CTCAE).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy
Official Title  ICMJE Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)
Brief Summary Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is dendritic cells transfected with mRNA of survivin, hTERT og autologous tumor stem cells derived from tumorspheres.
Detailed Description

Autologous leukapheresis for enrichment of PBMCs is performed after enrollment of the patient into the trial. Ex vivo generated DCs will be frozen and stored in the vapour phase of liquid nitrogen.

At first surgery, tumor biopsies will be cultured under sphere-forming conditions under ex vivo conditions for enrichment of glioblastoma stem cells. mRNA will purified and amplified from these autologous tumor stem cells.

At specified intervals patients randomized to the vaccine group will receive intradermal injections of DCs transfected with mRNA from autologous tumor stem cells, survivin and hTERT. Injections will be given as three separate injections at three separate sites.

Vaccination will be continued for as long as there are vaccines available.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open label, randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Biological: Dendritic cell immunization
    Intradermal injection
  • Drug: Adjuvant temozolomide
    After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days at 150 mg per square meter for the first cycle and thereafter increase to 200 mg per square meter beginning with the second cycle.
    Other Name: Standard therapy
Study Arms  ICMJE
  • Experimental: DC immunization
    Leukapheresis before start of radiotherapy. Immunization with DCs starting first week after finalizing radiotherapy (2Gy x 30) and concomitant temozolomide.
    Intervention: Biological: Dendritic cell immunization
  • Active Comparator: Standard therapy
    Radiotherapy (2 Gy x30) with concomitant and adjuvant temozolomide.
    Intervention: Drug: Adjuvant temozolomide
Publications * Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tønnesen P, Suso EM, Sæbøe-Larssen S, Sandberg C, Brinchmann JE, Helseth E, Rasmussen AM, Lote K, Aamdal S, Gaudernack G, Kvalheim G, Langmoen IA. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother. 2013 Sep;62(9):1499-509. doi: 10.1007/s00262-013-1453-3. Epub 2013 Jul 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2023
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

All of the following conditions must apply:

  • Must be at least 18 years and less than 70 years of age.
  • Must be ambulatory with a ECOG performance status 0 or 1
  • Must have histologically confirmed glioblastoma IDH wild-type, with unmethylated MGMT-gene promotor, and a candidate for combined radiation therapy and chemotherapy ("Stupps Regimen").
  • Must have accessible volume and quality of tumor tissue for vaccine production (proliferation of cells and extraction of tumor mRNA) at first surgery.
  • Must have postoperative MRI after surgery with contrast enhancing tumor remnant of less than 1 cm3 or less than 10% of original tumor volume.
  • Normal organ function defined by laboratory values as following: ANC > 1.5 x 109/L; platelets >100 x109/L, Hb >9g/dL (> 5.6 mmol/L). Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance >40 mL/min, Bilirubin < 20% above the upper limit of normal, ASAT and ALAT < 2.5 the upper limit of normal. Albumin >2.5 g/L.
  • Serology indicating contagious HIV, HBV, HCV and Treponema pallidum must be negative.
  • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria:

  • Tumor in a localization where a modest increase in size due to reactive oedema may have a large impact on the patient's neurological condition, i.e. brain stem.
  • History of prior malignancy other than glioblastoma, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and ca. cervicis stage IB.
  • Active infection requiring antibiotic therapy.
  • Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.
  • Prior splenectomy.
  • Glucocorticoid treatment not possible to terminate due to autoimmune disease or increased intracranial pressure.
  • Adverse reactions to vaccines such as asthma, anaphylaxis or other serious reactions.
  • History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
  • Chemotherapy or other potentially immune-suppressive therapy outside protocol that has been administered within the last 4 weeks prior to vaccination.
  • Positive pregnancy test in women of childbearing potential (within 7 days before the first vaccination). Women of childbearing potential and sexually active male participants must use reliable methods of contraception during the whole treatment period and 3 months after the last trial drug dose. Reliable methods of contraception are defined in section .
  • Any reason why, in the opinion of the investigator, the patient should not participate.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Einar O Vik-Mo, MD, PhD +47 23074340 uxvieb@ous-hf.no
Contact: Soveig Bringsli solbri@ous-hf.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03548571
Other Study ID Numbers  ICMJE DEN-STEM
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Einar Vik-Mo, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Iver A Langmoen, MD, PhD Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP