Temozolomide for Glioblastoma

Inclusion criteria

• {"criterion_text":"- Histologically confirmed glioblastoma\n- Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments\n- The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of IRST IRCCS and must fulfil all the acceptance criteria prescribed by the GMP procedures\n- Availability of sufficient leukapheretic material for the preparation of the vaccine product\n- Karnofsky performance status (KPS) ≥ 70% or performance status of 0 or 1 on the ECOG Performance Scale\n- Be willing and able to provide written informed consent/assent for the trial\n- Be ≥ 18 years of age on day of signing informed consent\n- Life expectancy greater than 12 weeks\n- Patients must have normal organ and marrow function\n- Female participants of child bearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 4 months thereafter."}

Exclusion criteria

• {"criterion_text":"- Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment\n- Patient with a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 20 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment\n- Medical history of severe acute or chronic disease with poor prognosis, autoimmune disorder, immunodeficiency or organ allograft\n- Known history of active TB (Bacillus Tuberculosis)\n- Previous treatment with a cancer vaccine.\n- Known allergy or intolerability to components of vaccine, to TMZ\n- Severe myelosuppression\n- History of bleeding diathesis or coagulopathy\n- O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status equivocal\n- Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery\n- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n- Has known history of, or any evidence of active, non-infectious pneumonitis or interstitial lung disease\n- Has an active infection requiring systemic therapy\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n- Any known history of or is positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous. The sole positivity for antibodies against the HBsAg (i.e. with all other HBV markers negative) is indicative of previous HBV vaccination and therefore is acceptable\n- Has received a live vaccine within 30 days of planned start of study therapy. (Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed)"}

Primary endpoints

• {"endpoint_text":"- Progression free survival (PFS), measured as the proportion of patients without progression of disease at three months from leukapheresis","definition_or_measurement_approach":"Measured as the proportion of patients without progression of disease at three months from leukapheresis (proportion free from progression at 3 months)."}
• {"endpoint_text":"- Proportion of patients experienced grade 3 or higher adverse events related to the study treatment","definition_or_measurement_approach":"Measured as the proportion of patients experiencing grade 3 or higher adverse events related to the study treatment (safety/tolerability assessed by CTCAE grades)."}

Secondary endpoints

• {"endpoint_text":"- Evaluation of the prognostic role of a positive DTH test after at least four vaccine administrations","definition_or_measurement_approach":"Assessment of prognostic role of positive delayed-type hypersensitivity (DTH) test after ≥4 vaccine administrations."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from defined baseline to death from any cause."}
• {"endpoint_text":"- Ability to enhance the proportion of circulating immune effectors specific for tumor antigens; evaluation of the persistence of an anti-tumor immune response; determination of plasma levels of a panel of inflammatory cytokines and proangiogenic factors; evaluation of the prognostic and predictive role of tumor antigen expression in tumor tissue; analysis of the prognostic and predictive role of immune cells in the peripheral blood and in the tumor microenvironment","definition_or_measurement_approach":"Immunological and biomarker assessments including proportion/persistence of circulating tumor-specific immune effectors, plasma cytokine/pro-angiogenic factor levels, tumor antigen expression in tissue, and immune cell analyses in peripheral blood and tumor microenvironment as described in protocol."}

Italy

Earliest CTIS Part Ii Submission Date

17-06-2024

Latest Decision Or Authorization Date

15-07-2024

Processing Time Days

28

Number Of Sites

1

Number Of Participants

28

Primary sponsor

Full Name

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy