metastatic melanoma MedDRA version: 15.1 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: 15.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: INTRONA*SC IV 1FL 18MUI 3ML
Pharmaceutical Form: Injection
INN or Proposed INN: INTERFERON ALFA-2B
Concentration unit: million IU million international units
Concentration type: equal
Conc
Sponsors
ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
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 malignant unresectable stage III or stage IV melanoma; 4. Patients must have a minimum of two lesions, one of which must be measurable,(i.e. that can be accurately measured in two perpendicular dimensions, with at least 1 diameter >20 mm and the other dimension >10 mm with conventional techniques or at least 10 x 10 mm with spiral CT scan). 5. Pretreated brain metastases which have been clinically stable for at least 6 months and not requiring corticosteroids are allowed; 6. ECOG performance status 0-1 ; 7. 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); 8. Prior lines of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have lasted prior treatments at least 4 weeks before the first vaccine dose); 9. Men and women aged 18-70 years. 10.Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up 8 weeks after the study, in order to minimize the risk of pregnancy; 11. Patients must have normal organ and marrow function as defined below: - leukocytes >1,500/microL - absolute neutrophil count >1,000/microL - platelets >80,000/microL - total bilirubin within 2 x ULN - AST(SGOT)/ALT(SGPT) =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate/homogenate preparation). 2. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 3. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. 4. Patients with known progressing and/or symptomatic brain metastases. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (on physician’s judgment). 6. Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix); 7. Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1- Clinical objective: to select the regimen that has the best immune related Disease Control Rate (irDCR) in the different external immunostimulant conditions utilized in combinations with autologous tumor lysate loaded DC vaccine. 2- Immunological objective: to compare between the different treatment arms the immunologic efficacy, defined as the proportion of subjects developing positive DTH to ATL and/or KLH, combined with quantification of tumor antigen-specific circulating immune effectors performed by IFN?-ELISPOT analysis at the base line and after at least 4 immunizations, if DTH analysis will not detect differences in terms of immunologic efficacy between the different arms.;Secondary Objective: - To assess safety, tolerability and feasibility of the different external immunostimulant combinations. - To evaluate the effects of preleukapheresis IFN-alfa on: a) Dendritic Cells yield b) Dendritic Cells potency c) TEM-8 upregulation at the mRNA level upon Dendritic Cells maturation. - To estimate immune-related Disease Control Rate (irDCR) in the whole series and in the different treatment arms, and to compare irDCR in the two different immunomodulating conditions (IFN-alfa vs Radiotherapy). - To further define the clinical efficacy of the different treatment arms.;Primary end point(s): The clinical objective is to select the regimen with the best Disease Control Rate (irDCR) in different external immunostimulants conditions in combination with the Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate; The immunological objective is to compare the immunological activity among the different treatment arms, defined as the proportion of subjects who develop sensitization against tumor lysate and / or KLH protein (Key-Hole Lympet hemocyanin), combined with the quantification of antitumor circulating immune effectors after at least 4 doses of vaccine.;Timepoint(s) of evaluation of this end point: 36 m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical endpoints: a) overall rate of adverse events recorded in each treatment group up to 30 days after vaccination b) irDCR in the different treatment arms and comparison between the two different conditions immunomodulatory (IFN and Radiotherapy). c) clinical activity: OS (Overall Survival), irTTP (immune-related Time To Progression), irORR (immune-related Overall Response Rate), irDOR (immune-related Duration Of Response), irTTR (immune-related Response Time To ) and irPFS (immune-related Progression Free Survival) Biological endpoints: a) effects of IFN-alpha pre-leukapheresis yield of vaccine b) effect of IFN-alpha pre-leukapheresis on the potency of dendritic cells, ie on the ability to co-stimulation of dendritic cells. c) Evaluation of the maturation of dendritic cells induced by the upregulation of TEM-8 expression;Timepoint(s) of evaluation of this end point: 36 months | — |
Countries
Italy
Contacts
Public Contactdata manager
IRST
Outcome results
None listed