Randomized Comparative Study for Efficacy and Safety Evaluation of HLA-haploidentical Hematopoietic Cell Transplantation With or Without Post-transplant Allogeneic Donor-derived Natural Killer Cell Infusion in High-risk Acute Myelogenous Leukemia and Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 77
- 试验地点
- 2
- 主要终点
- number of patients who experience progression/recurrence of AML after HCT
研究概览
简要总结
This is a single center, open label, random comparison phase 2b study. The primary objective of this study is, by random comparison, to assess the anti-leukemia effect of allogeneic, donor-derived natural killer (NK) cells infused after HLA-haploidentical hematopoietic cell transplantation (HCT) in patients with refractory acute myelogenous leukemia (AML).
The secondary objectives of the study are to assess the side effects of donor NK cell infusion, effects of donor NK cell infusion upon HCT outcomes, as well as effects upon post-HCT immune recovery.
详细描述
5.0 Study design
5.1. Study patient should be enrolled by PI Kyoo-Hyung Lee, MD or Young-Shin Lee, RN.
5.2. Random assignment 5.2.1. Patients were randomly assigned to study arms the day before initiation of conditioning therapy (day -8).
5.2.2. Stratification Refractory AML Stratification 1: Primary refractory vs. relapse-refractory/2 or more relapse Stratification 2: peripheral blood blast <5% vs. ≥5% 5.2.3. extra leukapheresis will be performed form donors assigned to treatment cohort.
High-risk AML Stratification: AML in CR1 with high-risk features vs. AML CR2
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
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with refractory AML Refractory AML is defined as follows;
- •Primary refractory: failure to achieve complete remission (CR) after 2 cycles of induction chemotherapy; or, in patient ≥65 years of age, progressive AML after treatment with hypomethylating agent (increase in peripheral blood blast by 50% or increase in bone marrow blast by 25%)
- •Relapse then refractory: recurrence of AML, which is refractory to standard salvage chemo therapy; or, in patient ≥65 years of age, to hypomethylating agent
- •AML in ≥2 relapses
- •Patients should be 19 years of age or older
- •Patients should have Karnofsky performance scale ≥70
- •Patients and cell donors must understand fully and sign informed consent forms
排除标准
- •Pregnant or lactating women
- •Patient with abnormal liver function (total bilirubin ≥ 5.0 mg/dl, AST ≥ 5 times upper normal limits)
- •Patients with abnormal renal function (creatinine ≥ 3.0 mg/dl)
- •Patients with clinically-evident cardiac or pulmonary dysfunction
- •Patients with infection that is progressive despite appropriate anti-microbial treatment
- •Patients with hypersensitivity to gentamicin
- •Patients who had received allogeneic cell therapy previously.
结局指标
主要结局
number of patients who experience progression/recurrence of AML after HCT
时间窗: up to 60 months
次要结局
- number of patients who achieve engraftment after HCT(up to 6 months)
- number of patients who develop acute GVHD(up to 4 months)
- number of patients who die after HCT without progression of AML(up to 60 months)
- number of patients who develop chronic GVHD(up to 60 months)
- number of patients who experience donor NK cell infusion-associated toxicity(up to 1 month)
研究者
Kyoo-Hyung Lee
MD, PROFESSOR, HEMATOLOGY
Asan Medical Center