First in Human Pilot Study to Assess the Safety and Efficacy of Dendritic Cells Loaded With Frameshift Derived Neopeptides for the Prevention of Cancer in of Lynch Syndrome Carriers
Tha aim of this clinical trial is to evaluate safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells. Immunogenicity of the prduct(DC-DELAY) will be evaluated also.
• Individuals that are carriers of a pathogenic or likely pathogenic germline variant in one of the mismatch repair genes (MLH1, MSH2, MSH6).
• Participants must have no evidence of active or previous invasive cancer.
• Participants must have endoscopically accessible colon.
• Participants must consent to follow the standard of care surveillance with colonoscopy and biopsies every 1-2 years.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥70%).
• Haemoglobin ≥10 g/dL or haematocrit ≥30%; Leukocyte count ≥3.0x109/l; Platelet count ≥100x109/l; Absolute neutrophil count ≥1.5x109/l; Absolut lymphocyte count ≥0.8x109/l.
• Creatinine clearance (calculated if measured is not available) ≥60mL/min/1.73m2.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\] ≤2 times the institutional upper limit of normal (ULN).
⁃ Total bilirubin ≤ 1.5 the ULN; participants with Gilbert's disease may be enrolled with higher total bilirubin if their direct bilirubin is ≤1.5 times the ULN.
⁃ Written informed consent.
⁃ Women of child-bearing potential\* must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods until one year following the las immunization dose. Highly effective contraceptive methods will include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence. \* A woman will be considered of childbearing potential, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as 0 menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient.