Advanced Translational Research on Childhood Leukemia

Childhood Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04478006
• Other study ID #: HKCH-REC-2020-012
• Status: Recruiting
• Start date: July 1, 2020
• Est. completion date: June 2025

Study information

• Verified date: September 2023
• Source: Chinese University of Hong Kong
• Contact: Kathy Chan, Ph. D.
• Phone: 852-35052858
• Email: kathyyychan[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Childhood Leukemia
• Leukemia

Intervention

Genetic:
• RNA-seq
Gene expression and fusion transcripts analysis
• whole exon sequencing
Genetic alternation analysis

Other:
• Cytogenetics test
Remission and relapse are monitored by cytogenetic analyses.

Locations

Country	Name	City	State
China	Hong Kong Children Hospital	Hong Kong	Hksar

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Gene expression profiles of childhood leukemia	Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.	Baseline
Primary	Drug sensitivity profiles	Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.	Baseline
Primary	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