Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.
详细描述
The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.
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 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients over the age of 18 year.
- •Patients diagnosed with advanced melanoma.
- •Patients that are considered candidates for ipilimumab therapy.
- •Patients able to understand and willing to sign a written informed consent documents.
- •Patients willing to have regular blood draws, one before treatment and four during or after treatment.
排除标准
- •Patients under the age of
- •Patients with Stage I or II, melanoma who are not candidates for Ipilimumab.
- •Patients that have received systemic treatments within four weeks prior to the beginning of treatment.
- •Women that are pregnant or nursing.
- •Patients taking immunosuppressive medications.
- •Patients with active autoimmune disease.
- •Patients with known sensitivity to retinoic acid derivatives.
- •Patients with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin > 2.5 × ULN.
研究组 & 干预措施
Ipilimumab
Arm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks.
干预措施: Ipilimumab (Drug)
VESANOID
Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment.
干预措施: VESANOID (Drug)
VESANOID
Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of Adverse Events
时间窗: Up to 2 years from the time of study enrollment for each patient.
Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.
MDSC Frequency
时间窗: 84 and 130 days following the first treatment
The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.
MDSC Suppressive Function
时间窗: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.
次要结局
- Changes in the Frequency of Tumor-specific T Cell Responses(4 weeks prior to start, Midway thru and at least 30 days post final infusion)
- Unresectable Stage III and STAGE IV(Up to 2 years from the time of study enrollment for each patient.)