Advanced Translational Research on Childhood Leukemia

The Chinese University of Hong Kong

Status: Enrolling

Conditions: Childhood Leukemia

Treatments: Genetic: RNA-seq; Other: Cytogenetics test; Genetic: whole exon sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT04478006

PAED-2024-082 (Other Identifier)

HKCH-REC-2020-012

Details and patient eligibility

About

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.

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

300 participants in 1 patient group

Childhood Leukemia

Description:

Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.

Treatment:

Genetic: whole exon sequencing

Other: Cytogenetics test

Genetic: RNA-seq