Driving Therapeutic Progress of Childhood Leukemia Through Advanced Translational Research With Immediate and Long-term Impact. Precision Medicine for Childhood Leukemia.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Antibody efficacy for treatment of childhood leukemia
研究概览
简要总结
Prognosis of children with leukemia, the most common pediatric cancer, has improved markedly. Yet, relapse still occurs in 15-40% of patients with a probability of survival of <50%, which is unlikely to be boosted by intensification of standard chemotherapy due to overwhelming toxicity. The advent of effective and safe targeted therapies for high-risk cases is therefore imperative. This study constitutes two research projects aiming at driving therapeutic advances.
详细描述
The first part of the study aimed to investigate genomics and drug sensitivity profiling of childhood leukemia and its potential application for precision medicine.
The second part of the study aimed to develop novel antibody for treatment of childhood leukemia by animal model experiments.
Design:
Project 1: Whole-exome and RNA sequencing will be performed on children with leukemia (ALL, AML, MPAL, JMML, MDS) prospectively recruited in the Hong Kong Children's Hospital. Samples will be screened for their sensitivity to preselected, clinically accessible targeted agents in an ex vivo culture system. Results for the high-risk patients will be subjected to the tumor broad for evaluation.
Project 2: Fully human antibody candidates identified by phage display will be engineered into therapeutic forms, and assessed for efficacy and safety in patient-derived xenografts of relapsed/refractory B-ALL and in transgenic mice. The mechanisms of action will be identified by single-cell RNA sequencing.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •List of inclusion criteria:
- •acute lymphoblastic leukemia (ALL) or
- •acute myeloid leukemia (AML) or
- •3 .mixed phenotype acute leukemia (MPAL) or
- •4. juvenile myelomonocytic leukemia (JMML) or
- •5. myelodysplastic syndromes (MDS) or
- •6. normal bone marrow donor
排除标准
- •This study will not recruit subjects who are unable to understand English or Chinese.
- •Patient or parent refusal
研究组 & 干预措施
Childhood Leukemia
Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.
干预措施: RNA-seq (Genetic)
Childhood Leukemia
Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.
干预措施: whole exon sequencing (Genetic)
Childhood Leukemia
Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.
干预措施: Cytogenetics test (Other)
结局指标
主要结局
Antibody efficacy for treatment of childhood leukemia
时间窗: Up to 1 year
In vitro biochemical and biological assays and invivo leukemic patient-derived xenografts are used to characterize the efficacy and toxicity of the novel human anitbodies.
Gene expression profiles of childhood leukemia
时间窗: Baseline
Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.
Drug sensitivity profiles
时间窗: Baseline
Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.
Genetic alterations of childhood leukemia
时间窗: Baseline
Association of mutation data with drug sensitivity profiles and disease-free survival /overall survival are analysed using standard statistical methods.
次要结局
未报告次要终点
研究者
Kathy Chan
Scientific Officer
Chinese University of Hong Kong