Complementary vaccination with dendritic cells pulsed with autologous tumor lysate in resected stage III and IV melanoma patients: a phase II randomized trial (ACDC adjuvant Trial)

INTERVENTION: Product Name: DC‐VACCINE_IRSTIRCCS Product Code: DC‐VACCINE_IRSTIRCCS Pharmaceutical Form: Suspension for injection INN or Proposed INN: DC‐VACCINE_IRSTIRCCS Current Sponsor code: DC‐VACCINE_IRSTIRCCS Concentration unit: Other Concentration type: range Concentration number: 7000000‐14000000 Trade Name: PROLEUKIN ‐ 18.000.000 UI POLVERE PER SOLUZIONE INIETTABILE O PER INFUSIONE 10 FLACONCINI IN VETRO DA 22.000.000 UI Product Name: IL2_IRSTIRCCS Product Code: IL2_IRSTIRCCS Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: ALDESLEUKIN CAS Number: 110942‐02‐4 Current Sponsor code: IL2_IRSTIRCCS Concentration unit: IU international unit(s) Concentration type: equal Concentration number: 3000000‐ CONDITION: resected stage III and IV melanoma ; MedDRA version: 20.0 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.0 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: RFS: relapse free survival is the time from the; date of randomization to the date of first relapse or the date of death from any cause or the date of the last restaging in non relapsed patients. Primary end point(s): RFS: relapse free survival is the time from the date of randomization to the date of first relapse or the date of death from any cause or the date of the last restaging in non relapsed patients. Secondary Objective: ‐ OS: Overall survival will be measured from the date of randomization until the date of death from any cause or the last date on which it was known that the patient was alive.; ‐In vivo and in vitro immunomonitoring.; Immunologic efficacy will be measured by best DTH score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses, alone or combined with IFN‐g ELISPOT analysis of tumor antigen‐specific circulating effectors obtained after a minimum of 4 vaccine doses, both compared with prevaccine samples. In vivo monitoring will focus on functional phenotyping of circulating immune effectors/regulators, functional characterization of circulating tumor antigen‐specific immune effectors and regulators, and identification of serum markers that are predictive of response.; ‐Toxicity; ‐Prognostic and predictive marker response; ‐Immunologic response Timepoint(s) of evaluation of this end point: 36 months SECONDARY OUTCOME: Secondary end point(s): ‐Immunologic response Timepoint(s) of evaluation of this end point: 36 months INCLUSION CRITERIA: 1.Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure. 2.Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the “Product Specification File”. 3.Patients must have histologically or cytologically confirmed melanoma (all type of melanomas); 4.Patients must be disease free after surgical removal of a metastatic lesions (stage IV or metacronouse stage III) 5.ECOG performance status 0‐1 6.Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before performing any of the GMP‐regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor lysate/homogenate preparation); 7.Men and women aged = 18 years. 8.Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up 8 weeks