Allogeneic Vaccine Modified to Express HLA A2/4-1BB Ligand for High Risk or Low Residual Disease Melanoma Patients - Phase I/II Study.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- grade 2-4 adverse events according to CTCEA criteria
研究概览
简要总结
This study is designed for patients who had malignant melanoma and, following tumor removal, are now free of disease, or have only very minor residual disease, and are at a very high risk of disease recurrence. These patients will be treated with the A2/4-1BBL melanoma vaccine, a compatible melanoma cell line that has been engineered to express a molecule termed 4-1BBL, which enhances the chances of the cell line to be recognized by the patient's immune system, and to induce its stimulation. The hypothesis that drives the study states that the immune response against the cell line will also be effective against the residual tumor that may still be present in the body.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients included in this protocol must carry one or more of the following tissue typing alleles: HLA-A2, -A24, -A33, -B35, -B49, -CW04/12(04/08). We estimate that 50% of melanoma patients will be eligible.
- •Cutaneous malignant melanoma AJCC stage IIb (>4 mm) or IIc (ulcerated melanoma >4mm).
- •Metastatic melanoma AJCC stage III (nodal involvement, N1-3a,b) post-surgical removal of lymph nodes.
- •Metastatic melanoma AJCC stage IV, completely resected.
- •Non-resectable metastatic melanoma of low burden disease and normal LDH who have undergone at least two treatment lines, including chemotherapy (DTIC, temodal, taxanes, platinum compounds), anti-CTLA-4 (ipilimumab) and B-RAF inhibitor if harboring the V600E BRAF mutation in their tumor.
- •Non cutaneous malignant melanoma of respective stages including uveal and mucosal melanoma.
- •Melanoma can be of either mutant or wild-type B-RAF.
- •Karnofsky performance status > 80 (Normal activity with effort).
- •No active cardio-respiratory disease.
- •Not pregnant or nursing. Women must take contraceptives during the treatment period.Hematocrit >25% and WBC >
- •Informed consent of the patient.
排除标准
- •Administration of cytotoxic drugs or extensive radiotherapy less than 28 days prior to protocol administration.
- •Active brain metastases requiring corticosteroids.
- •Concurrent malignancy (other than skin cancer, carcinoma in situ of cervix and early stage prostate cancer).
- •Active serious infection.
- •Allergy to penicillin.
- •Patient's will to withdraw from the study at any stage.
- •HIV and chronic hepatitis B and C carrier
研究组 & 干预措施
A2/4-1BBL melanoma vaccine
On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.
On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered at the day care unit. On day 14 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed. Four additional doses of the vaccine will be administered at intervals of 21 days.
干预措施: A2/4-1BBL melanoma vaccine (Biological)
A2/4-1BBL melanoma vaccine
On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.
On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered at the day care unit. On day 14 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed. Four additional doses of the vaccine will be administered at intervals of 21 days.
干预措施: DNP sensititzation (Procedure)
A2/4-1BBL melanoma vaccine
On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.
On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered at the day care unit. On day 14 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed. Four additional doses of the vaccine will be administered at intervals of 21 days.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
grade 2-4 adverse events according to CTCEA criteria
时间窗: month 6
monitoring anti-tumor immune response
时间窗: month 6
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
次要结局
- overall survival and disease free survival(D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5)