Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy
Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)
Oslo University Hospital
60 participants
Apr 26, 2018
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria9
- 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 Criteria11
- 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.
Interventions
Intradermal injection
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT03548571