Releasing the Brakes on CD8+ T Cells in the Melanoma Sentinel Lymph Node by Pre-operative Local Administration of Low-dose Anti-CTLA-4 (Tremelimumab)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 主要终点
- Number of participants with adverse events as assessed by CTCAE V3.0
研究概览
简要总结
This study evaluates the clinical safety and tolerability, and the immunological effects of local intradermal injection of tremelimumab in patients with clinical stage I/II melanoma patients undergoing a sentinel node biopsy (SNB). Patients will be treated by local intradermal injections around the excision site of the primary tumor with escalating doses of 2, 5, 10 or 20 mg tremelimumab.
详细描述
Although of limited therapeutic value, the SLN procedure has proven a useful prognostic tool for the assessment of melanoma relapse and mortality risk. Moreover, the SLN is of great value for the assessment of immunological interventions for melanoma. Since early melanoma development is accompanied by impaired immune effector functions primarily in the SLN, there is a strong rationale for therapeutic immune modulation of the SLN aimed at strengthening cellular immune functions.
The investigator now propose a phase I dose escalation study to administer intradermally a single clinical dose of tremelimumab/anti-CTLA-4 locally at the primary tumor excision site of patients with clinical stage I/II melanoma. Such a single local administration aimed at conditioning of the SLN should allow for the use of relatively low anti-CTLA-4 dosages without excess risk of autoimmune effects.
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
- •Age ≥ 18 years
- •Clinical stage I/II melanoma patients, planned to undergo a sentinel lymph node biopsy (SNB)
- •ECOG performance status 0 or 1
- •White blood count (WBC) ≥ 3 x10^9/L
- •Platelet count ≥ 100 x10^9/L
- •Hemoglobin ≥ 6.5 mmol/L
- •Serum creatinine ≤ 2.5 x ULN
- •Total serum bilirubin, AST, ALT and LDH ≤ 2x ULN
排除标准
- •Non-oncology vaccine therapy used for prevention of infectious diseases (up-to) 4 weeks prior and/r 8 weeks after any dose of tremelimumab
- •Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist
- •Uncontrolled infectious disease including negative testing for HIV, HBV, HCV
- •Autoimmune disease
研究组 & 干预措施
Tremelimumab
Intradermal injection of tremelimumab at the primary melanoma excision site, 7 days prior to sentinel node biopsy (SNB), with escalating doses of 2, 5, 10 or 20 mg tremelimumab (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients).
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Number of participants with adverse events as assessed by CTCAE V3.0
时间窗: From the time of injection until 28 days after injection of tremelimumab
The descriptions and grading scales of CTCAE V 3.0 will be utilized for all toxicity reporting
Change in frequency of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
时间窗: 7 days after the intradermal injection of tremelimumab
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in frequency of tumor-specific T-cells, Tregs and dendritic subsets will be assesess and compared to baseline (time of the injection of the intradermal injection)
Change in activation status of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
时间窗: 7 days after the intradermal injection of tremelimumab
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in expression level of surface antigens for tumor-specific T-cells, Tregs and dendritic subsets are analyzed and compared to baseline (time of injection of tremelimumab)
次要结局
未报告次要终点
研究者
A.J.M. van den Eertwegh
Principal Investigator
Amsterdam UMC, location VUmc