In modern practice a trimodality treatment has emerged as standard of care for histologically confirmed glioblastoma. We hypothesize that the additional vaccination against herpes zoster, after surgical resection followed by irradiation therapy and chemotherapy of patients with glioblastoma will lead to a superior local control, overall and progression free survival. In an additional experimental setting based on patient preference the immunological effectiveness of the adoptive transfer of autologous polyclonal cytomegalovirus (CMV) specific T cells will be examined.
This multicenter study investigates novel immunomodulatory strategies in patients with histologically confirmed glioblastoma undergoing microsurgical resection at initial diagnosis. In the randomized intervention arm, patients receive an EMA-approved, inactivated herpes zoster vaccine postoperatively, followed by standard radiotherapy or radiochemotherapy according to ESTRO/EANO guidelines. In a patient-preference experimental arm, the same regimen is combined with autologous CMV-specific T-cell adoptive transfer. The control group undergoes neurosurgical resection and standard-of-care radiotherapy, with or without temozolomide, without additional herpes zoster vaccination or CMV-specific T-cell therapy. Primary endpoint is overall survival (OS), while secondary endpoints include progression-free survival (PFS) and local tumor control, immunological response, safety, and tolerability. Exploratory endpoints incorporate patient-reported outcome measures (PROMs), assessing quality of life, cognitive function, and treatment-related symptoms. Interventions are delivered from surgical resection through completion of radiochemotherapy. We hypothesize that herpes zoster vaccination will improve survival and local tumor control, while adoptive CMV-specific T-cell therapy will provide additional immunotherapeutic benefit in this refractory glioblastoma population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Based on patient-preference patients receive autologous CMV-specific T-cells additionally to vaccination contra herpes zoster after completion of radio(chemo-)therapy. Patients included in the experimental arm shall be HLA typed. Up to 6 intravenous infusions of in vitro-expanded T cells at a dose of 2 × 107 cells/m2 body surface area every 2 to 4 weeks shall be administered after clinical assessment. Patients shall continue standard-of-care treatment with temozolomide if indicated. Where possible, administration of autologous T-cells shall be scheduled to fall between chemotherapy treatment weeks to avoid concurrent infusions
Standard of care treatment without additional vaccination
Overall Survival
Time frame: Overall survival defined as time from neurosurgical resection to death of any cause. Study time per subject from enrollment through the end of treatment after a maximum of 12 months (provided that additional CTx consolidation therapy is administered)
Overall survival
Time frame: From enrollment through the end of treatment after a maximum of 12 months (provided that additional CTx consolidation therapy is administered)
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Enrollment
230