Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oslo University Hospital
• Treatments: Dacarbazine; Temozolomide; Vaccines

Criteria

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.