Malignant Melanoma of Skin Stage III Clinical Trial
— ABSIDEOfficial title:
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumor Lysate or Homogenate Combined With Immunomodulating Radiotherapy and/or Preleukapheresis IFN-alfa in Patients With Metastatic Melanoma: a Randomized "Proof-of-principle" Phase II Study
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study. Study Design: Randomized selection design, proof of principle study Study Duration: 36 months Number of Subjects: 24 evaluable patients Diagnosis and Main Inclusion Criteria: Patients with non resectable stage III or stage IV malignant melanoma carrying at least 2 measurable lesions, any line after 1st line Vemurafenib in patients carrying BRAF mutation-positive melanoma and/or ≥ 2nd line Ipilimumab. Study Product, Dose, Route, Regimen and duration of administration: Intradermal Autologous Dendritic Cell vaccine loaded with autologous tumor lysate or homogenate on weeks 1, 4 6 and 8 during induction phase, and every 4 weeks during maintenance phase up to a maximum of 14 vaccine doses (each dose followed by IL-2 3 MU day 2-6) COMBINED OR NOT WITH - IFN-alfa 3 MU daily for 7 days before leukapheresis AND/OR - Three daily doses of 8 Gy up to 12 Gy delivered to one metastatic field between vaccine doses 1 and 2 (optional to one additional field between doses 7 and 8) utilizing IMRT-IMAT techniques.
| Status | Recruiting |
| Enrollment | 24 |
| Est. completion date | August 2021 |
| Est. primary completion date | March 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 70 Years |
| Eligibility | 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. Patients carrying BRAF mutation-positive melanoma must have received previous Vemurafenib, unless they are not eligible or refuse the treatment. 6. Patients treated with previous first line therapy must have received Ipilimumab, unless they are not eligible or refuse the treatment. 7. Pretreated brain metastases which have been clinically stable for at least 6 months and not requiring corticosteroids are allowed; 8. ECOG performance status 0-1; 9. 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); 10. 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); 11. Men and women aged 18-70 years. 12. 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; 13. 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) <2.5 x ULN - creatinine = 2 mg/dl 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 with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment. 3. Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this treatment. 4. 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. 5. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. 6. Patients with known progressing and/or symptomatic brain metastases. 7. 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). 8. 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); 9. Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy). |
| Country | Name | City | State |
|---|---|---|---|
| Italy | UO Immunoterapia e laboratorio TCS, IRST IRCCS | Meldola | FC |
| Lead Sponsor | Collaborator |
|---|---|
| Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Safety, tolerability and feasibility assessments | Evaluation of safety, tolerability and feasibility of the experimental treatments through the determination of the percentage of patients in each treatment group reporting an AE up to 30 days after vaccination. | 36 months | |
| Primary | immune related Disease Control Rate (irDCR) | The irDCR, defined as the proportion of subjects showing irBOR (immuno-related Best Overall Response) of confirmed irCR (immuno-related Complete Response), irPR (immuno-related Partial Response), or irSD (immuno-related Stable Disease), will be compared in the different treatment arms, with the aim to select the most effective treatment combination. | 36 months | |
| Primary | immunologic efficacy | The immunologic efficacy will be evaluated through DTH (Delayed Type Hypersensitivity) and IFN-gamma ELISPOT analysis of circulating antitumor effectors, after at least 4 induction doses of vaccination. | 36 months | |
| Secondary | biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) yield | DC yield will be evaluated as the number of vaccinating DC obtained per ml of leukapheretically processed blood from each leukapheresis. | 36 months | |
| Secondary | Overall Survival (OS) | OS is defined by median survival and survival rates at 1 and 2 year of follow-up) and will be compared in the different treatment arms | 36 months | |
| Secondary | immuno-related Time To Progression (irTTP) | irTTP is the time from randomization to the first date of documented irPD (immuno-related Progressive Disease) or death and will be compared in the different treatment arms | 36 months | |
| Secondary | immuno-related Overall Response Rate (irORR) | irORR is the proportion of treated subjects with a irBOR (immuno-related Best Overall Response) of confirmed irCR (immuno-related Complete Response) or confirmed irPR (immuno-related Partial Response). It will be compared in the different treatment arms. | 36 months | |
| Secondary | immuno-related Duration of Response (irDOR) | irDOR is defined as the time between the date of the first irCR (immuno-related Complete Response) or irPR (immuno-related Partial Response) and the date of irPD (immuno-related Progressive Disease) or death. It will be compared in the different treatment arms. | 36 months | |
| Secondary | immuno-related Time To Response (irTTR) | irTTR is defined as the time from first dosing date until the first irPR (immuno-related Partial Response) or irCR (immuno-related Complete Response). It will be compared in the different treatment arms. | 36 months | |
| Secondary | immuno-related Progression free Survival (irPFS) | irPFS is defined as the time between the first dosing date and the date of irPD (immuno-related Progressive Disease), or date of death. It will be compared in the different treatment arms. | 36 months | |
| Secondary | biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) potency | DC potency will be evaluated by a validated assay measuring the costimulatory ability of the vaccine (ELISPOT-COSTIM assay). | 36 months | |
| Secondary | biological effects of preleukapheresis IFN-alfa on TEM-8 upregulation at the mRNA level upon DC (Dendritic Cells) maturation | TEM-8 upregulation at the mRNA level upon DC maturation will be investigated by flow cytometry and real-time PCR. | 36 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02142335 -
Rituxan and Abraxane for the Treatment of Patients With Inoperable Stage III and IV Malignant Melanoma
|
Phase 2 |