Advanced Translational Research on Childhood Leukemia

Driving Therapeutic Progress of Childhood Leukemia Through Advanced Translational Research With Immediate and Long-term Impact. Precision Medicine for Childhood Leukemia.

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.

Study Overview

• Status: Recruiting
• Conditions: Childhood Leukemia
• Intervention / Treatment: Genetic: RNA-seq; Genetic: whole exon sequencing; Other: Cytogenetics test

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Kathy Chan, Ph. D.; Phone Number: 852-35052858; Email: kathyyychan@cuhk.edu.hk
• Study Contact Backup: Name: Kam Tong LEUNG, Ph. D.; Phone Number: 852-35133176; Email: ktleung@cuhk.edu.hk

Study Locations

• China
  • Hksar
    • Hong Kong, Hksar, China
      • Recruiting
      • Hong Kong Children Hospital
      • Contact: Kam Tong LEUNG, Ph. D.; Phone Number: 852-35133176; Email: ktleung@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Children suspected or diagnosed with leukemia at presentation will be recruited for the study.

Description

List of inclusion criteria:

1. acute lymphoblastic leukemia (ALL) or
2. 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:

1. This study will not recruit subjects who are unable to understand English or Chinese.
2. Patient or parent refusal

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Childhood Leukemia; Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic alterations of childhood leukemia	Association of mutation data with drug sensitivity profiles and disease-free survival /overall survival are analysed using standard statistical methods.	Baseline
Gene expression profiles of childhood leukemia	Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.	Baseline
Drug sensitivity profiles	Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.	Baseline
Antibody efficacy for treatment of childhood leukemia	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.	Up to 1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Kam Tong Leung, Ph. D., Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Investigative Techniques; Genetic Techniques; High-Throughput Nucleotide Sequencing; Sequence Analysis; Gene Expression Profiling; Sequence Analysis, RNA; RNA-Seq
• Other Study ID Numbers: HKCH-REC-2020-012; PAED-2024-082 (Other Identifier: IRB Central)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No