Advanced Translational Research on Childhood Leukemia
- Conditions
- Childhood Leukemia
- Interventions
- Genetic: RNA-seqGenetic: whole exon sequencingOther: Cytogenetics test
- Registration Number
- NCT04478006
- Lead Sponsor
- Chinese University of Hong Kong
- Brief Summary
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.
- Detailed Description
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.
Significance:
Implementation of functional genomics could identify leukemia patients who will benefit from targeted therapies and enable tailoring of precision medicine. The invented antibodies could be moved forward into clinical trials for salvaging high-risk pediatric B-ALL. Immediate and long-term impact on therapy of childhood leukemia is foreseen.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Childhood Leukemia Cytogenetics test Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment. Childhood Leukemia RNA-seq Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment. Childhood Leukemia whole exon sequencing Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.
- Primary Outcome Measures
Name Time Method Antibody efficacy for treatment of childhood leukemia 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 Baseline Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.
Drug sensitivity profiles Baseline Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.
Genetic alterations of childhood leukemia Baseline Association of mutation data with drug sensitivity profiles and disease-free survival /overall survival are analysed using standard statistical methods.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Hong Kong Children Hospital
🇨🇳Hong Kong, Hksar, China