Clinical trial NCT04478006: Advanced Translational Research on Childhood Leukemia
Official title: Driving Therapeutic Progress of Childhood Leukemia Through Advanced Translational Research With Immediate and Long-term Impact
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Childhood Leukemia
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 150
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children suspected or diagnosed with leukemia at presentation will be recruited for the study.

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.

Eligibility 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

Primary outcomes:
measure: Genetic alterations of childhood leukemia
timeFrame: Baseline
measure: Gene expression profiles of childhood leukemia
timeFrame: Baseline
measure: Drug sensitivity profiles
timeFrame: Baseline
measure: Antibody efficacy for treatment of childhood leukemia
timeFrame: Up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Hong Kong Children Hospital
state: Hksar
Study officials:
affiliation: Chinese University of Hong Kong
name: Kam Tong Leung, Ph. D.
role: PRINCIPAL_INVESTIGATOR
References: