Phase I/II Study of Haploidentical Natural Killer Cell Infusion in Patients With Refractory or Relapsed Malignant Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- To determine the maximum-tolerated dose of haploidentical NK cells
研究概览
简要总结
We hypothesized that haploidentical NK cells kill tumor cells more efficiently than autologous NK cells, based on the missing-self hypothesis. Therefore, we performed this study to investigate the role of haploidentical NK cell therapy in patients with refractory or relapsed malignant melanoma.
详细描述
Human NK cells recognize and kill transformed cells in a MHC-unrestricted fashion, suggesting the role of cancer immunotherapy. However, autologous NK cells showed the lack of significant clinical effects, because they are inhibited by self MHC class I molecules, based on the missing-self hypothesis. Contrarily, haploidentical NK cells with KIR-ligand incompatibility can mediate graft-versus-leukemia effect and protect patients with acute myelogenous leukemia (AML) from graft-versus-host disease. In addition, adoptive transfer of haploidentical NK cells following high-intensity conditioning induced complete remission (26%) in poor-prognosis AML patients. Thus, this study was designed to investigate the role of adoptive NK cell therapy in patients with refractory or relapsed malignant melanoma using CD3+ depleting CliniMACS® system.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic or relapsed malignant melanoma
- •Patients who received prior chemotherapy or immunotherapy
- •Patients who have at least one haploidentical donor willing to donate
- •ECOG performance status 0 or 1
- •18 - 75 years
- •At least one measurable disease according to the RECIST criteria
- •Patients with 45% or more left ventricular ejection fraction
- •Patients with 50% or more predicted DLCO
- •Adequate bone marrow function: absolute neutrophil count ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; and hemoglobin ≥ 9 g/dL
- •Adequate liver function: total bilirubin ≤ 1.0 x upper limit of the normal range (ULN); AST/ALT ≤ 2.5 x ULN; and alkaline phosphatase ≤ 2.5 x ULN
- •Adequate renal function: serum creatinine ≤ 1.0 x ULN or creatinine clearance ≥ 60 mL/min/1.73m2
- •At least 3 months of expected survival
- •Patients who signed informed consent
排除标准
- •Patients who received other chemotherapeutic agents within 30 days prior to study enrollment
- •Patients who received adoptive cell therapy including hematopoietic stem cell transplantation
- •Patients infected with HIV, HBV, or HCV
- •Hypersensitivity to cyclophosphamide or interleukin-2
- •Patients who received organ transplantation
- •Patients who had arrhythmia or ischemic heart disease
- •Pregnant or lactating women
- •Patients with uncontrolled infection who did not respond to appropriate antimicrobial agents
结局指标
主要结局
To determine the maximum-tolerated dose of haploidentical NK cells
时间窗: 1 year
次要结局
- To assess NK cell infusion-related toxicity(2 years)
- To evaluate response rate(2 years)
- To determine immune reconstitution after NK cell infusion(2 years)