Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)
Trial ID: NCT03548571
Interventional - Phase 2/3 - Unknown status
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.
Conditions
Interventions
- Dendritic cell immunization
- Adjuvant temozolomide
Eligibility
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.
Sponsor
Oslo University Hospital
Source: ClinicalTrials.gov
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