Dose-escalation Study to Assess the Safety and Tolerability of Sub-cutaneous Injections of a Peptide-loaded Plasmacytoid Dendritic Cell Line (GeniusVac-Mel4) in Patients With Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Tolerability and safety of a multiple sub-cutaneous injections of GeniusVac-Mel4.
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of multiple sub-cutaneous injections of GeniusVac-Mel4, a dendritic cell-based cancer vaccine, in patients with melanoma. The secondary objectives are to determine immune response and clinical efficacy of such injections in patients with melanoma.
详细描述
GeniusVac-Mel4 is a drug product composed of an irradiated allogeneic plasmacytoid dendritic cell (PDC) line loaded with 4 melanoma peptides derived from Melan-A, gp100, Tyrosinase or Mage-A3. This cell line is HLA-A*02:01, a phenotype found in 40% of the European population. This approach exploits the PDC line high capacity of boosting anti-tumor cytotoxic response against melanoma antigens in HLA-A*02:01 melanoma patients. In the preclinical studies, a strong proof of concept was brought. Indeed, the GeniusVac-Mel4 capacity to induce high number of cytotoxic antitumor T-cells was shown in melanoma model, both in vivo in humanized mice and ex vivo with patients' PBMC (peripheral blood mononuclear cells) (Aspord et al 2010 and 2012).
It is planned to include patients in three dose-escalating groups (4, 20, 60 millions of GeniusVac-Mel4 cells). At least, 3 patients will be recruited in each dose group of the trial.
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
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed metastatic melanoma (at stage IIIC or stage IV under the AJCC 2009 classification not surgically resectable.
- •Patients who do not respond to at least one line of systemic treatment
- •Male and female (with β-HCG negative test)
- •Patients HLA-A*0201
- •Age > 18 years
- •Blood parameters (Hemoglobin ≥ 10g/dl, Leucocytes ≥ 4000/μl,Lymphocytes ≥ 1000/μl, Platelets ≥100.000/μl, creatinin ≤ 2.0mg/dl, bilirubin ≤ 2.0mg/dl, ASAT and ALAT ≤ 2.5 fold the upper normal level)
- •OMS performance score < 3
- •Informed written consent.
排除标准
- •Positive serology for HCV, HTLV, HIV, active hepatitis
- •Protected persons according to French regulations articles L1121-5 to L1121-8 (Public Health Code)
- •Non-pregnant women without effective contraception
- •Any serious acute or chronic illness, for example: active infection, coagulation disorder.
- •Presence of a second cancer in the 5 years preceding inclusion into the study with the exception of in situ cervical carcinoma or a cutaneous carcinoma or other melanoma.
- •Intercurrent disease requiring corticosteroids.
- •Any active autoimmune disease including insulin dependent diabetes mellitus. Vitiligo or autoimmune thyroid disease are not criteria for exclusion.
- •Autoimmune eye disease.
- •Evidence of immunosuppression for any reason
- •Primary ocular melanoma
- •Chemotherapy, immunotherapy or radiotherapy in the 4 weeks preceding inclusion (6 weeks in the case of nitroso-urea and mitomycin C).
- •Treatment with drugs under development within 4 weeks.
- •Cerebral metastases metastasis with the exception of: known metastasis previously treated by surgery or stereotactic radio-surgery, AND Cerebral metastasis, if still present, must be stable for at least 90 days before inclusion and documented with two consecutive MRI or scanner with contrast media, AND, asymptomatic
- •Existence of any surgical or medical condition which, in the judgment of the Investigator, might interfere with this study.
- •Patients who are not willing to comply with the provisions of this protocol.
研究组 & 干预措施
GeniusVac-Mel4
Sub-cutaneous injections of GeniusVac-Mel4 in patients with melanoma.
干预措施: GeniusVac-Mel4 (Biological)
结局指标
主要结局
Tolerability and safety of a multiple sub-cutaneous injections of GeniusVac-Mel4.
时间窗: 1 year
Safety and tolerance is monitored by performing clinical laboratory tests, assessments of vital signs, full clinical examination, occurrence of adverse events.
次要结局
- Evaluation of the clinical response(1 year)
- Evaluation of the immune response(1 year)