Advanced Translational Research on Childhood Leukemia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: RNA-seq, whole exon sequencing, Cytogenetics test.
- Who it may be relevant to
- Registry conditions: Childhood Leukemia. Basic parameters: up to 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Driving Therapeutic Progress of Childhood Leukemia Through Advanced Translational Research With Immediate and Long-term Impact. Precision Medicine for Childhood Leukemia.
Overview
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.
Interventions
- Genetic RNA-seq
Gene expression and fusion transcripts analysis - Genetic whole exon sequencing
Genetic alternation analysis - Other Cytogenetics test
Remission and relapse are monitored by cytogenetic analyses.
Primary outcome measures
- Genetic alterations of childhood leukemia [Time frame: Baseline]
- Gene expression profiles of childhood leukemia [Time frame: Baseline]
- Drug sensitivity profiles [Time frame: Baseline]
- Antibody efficacy for treatment of childhood leukemia [Time frame: Up to 1 year]
Eligibility criteria
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
List of exclusion criteria:
- This study will not recruit subjects who are unable to understand English or Chinese.
- Patient or parent refusal
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
China · 1 center
- Hong Kong Children Hospital — Hong Kong
Identifiers
NCT: NCT04478006 · HKCH-REC-2020-012 · PAED-2024-082