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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Safety, tolerability and feasibility assessments
研究概览
简要总结
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.
详细描述
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.
Short Title/Acronym: ABSIDE (ABScopal effect-Interferon alpha-DEndritic cells)
Protocol Code IRST172.02
Phase: phase II clinical trial
Study Design: Randomized selection design, proof of principle study
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
- •Patients must have histologically or cytologically confirmed malignant unresectable stage III or stage IV melanoma;
- •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).
- •Patients carrying BRAF mutation-positive melanoma must have received previous Vemurafenib, unless they are not eligible or refuse the treatment.
- •Patients treated with previous first line therapy must have received Ipilimumab, unless they are not eligible or refuse the treatment.
- •Pretreated brain metastases which have been clinically stable for at least 6 months and not requiring corticosteroids are allowed;
- •ECOG performance status 0-1;
- •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);
- •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);
- •Men and women aged 18-70 years.
- •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;
- •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
排除标准
- •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).
- •Patients with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment.
- •Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this treatment.
- •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.
- •Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- •Patients with known progressing and/or symptomatic brain metastases.
- •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).
- •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);
- •Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy).
结局指标
主要结局
Safety, tolerability and feasibility assessments
时间窗: 36 months
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.
immune related Disease Control Rate (irDCR)
时间窗: 36 months
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.
immunologic efficacy
时间窗: 36 months
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.
次要结局
- Overall Survival (OS)(36 months)
- immuno-related Overall Response Rate (irORR)(36 months)
- biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) yield(36 months)
- immuno-related Time To Response (irTTR)(36 months)
- biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) potency(36 months)
- biological effects of preleukapheresis IFN-alfa on TEM-8 upregulation at the mRNA level upon DC (Dendritic Cells) maturation(36 months)
- immuno-related Time To Progression (irTTP)(36 months)
- immuno-related Progression free Survival (irPFS)(36 months)
- immuno-related Duration of Response (irDOR)(36 months)