<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04478006</url>
  </required_header>
  <id_info>
    <org_study_id>HKCH-REC-2020-012</org_study_id>
    <nct_id>NCT04478006</nct_id>
  </id_info>
  <brief_title>Advanced Translational Research on Childhood Leukemia</brief_title>
  <official_title>Driving Therapeutic Progress of Childhood Leukemia Through Advanced Translational Research With Immediate and Long-term Impact</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prognosis of children with leukemia, the most common pediatric cancer, has improved markedly.&#xD;
      Yet, relapse still occurs in 15-40% of patients with a probability of survival of &lt;50%, which&#xD;
      is unlikely to be boosted by intensification of standard chemotherapy due to overwhelming&#xD;
      toxicity. The advent of effective and safe targeted therapies for high-risk cases is&#xD;
      therefore imperative. This study constitutes two research projects aiming at driving&#xD;
      therapeutic advances.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The first part of the study aimed to investigate genomics and drug sensitivity profiling of&#xD;
      childhood leukemia and its potential application for precision medicine.&#xD;
&#xD;
      The second part of the study aimed to develop novel antibody for treatment of childhood&#xD;
      leukemia by animal model experiments.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Project 1: Whole-exome and RNA sequencing will be performed on children with leukemia (ALL,&#xD;
      AML, MPAL, JMML, MDS) prospectively recruited in the Hong Kong Children's Hospital. Samples&#xD;
      will be screened for their sensitivity to preselected, clinically accessible targeted agents&#xD;
      in an ex vivo culture system. Results for the high-risk patients will be subjected to the&#xD;
      tumor broad for evaluation.&#xD;
&#xD;
      Project 2: Fully human antibody candidates identified by phage display will be engineered&#xD;
      into therapeutic forms, and assessed for efficacy and safety in patient-derived xenografts of&#xD;
      relapsed/refractory B-ALL and in transgenic mice. The mechanisms of action will be identified&#xD;
      by single-cell RNA sequencing.&#xD;
&#xD;
      Significance:&#xD;
&#xD;
      Implementation of functional genomics could identify leukemia patients who will benefit from&#xD;
      targeted therapies and enable tailoring of precision medicine. The invented antibodies could&#xD;
      be moved forward into clinical trials for salvaging high-risk pediatric B-ALL. Immediate and&#xD;
      long-term impact on therapy of childhood leukemia is foreseen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Genetic alterations of childhood leukemia</measure>
    <time_frame>Baseline</time_frame>
    <description>Association of mutation data with drug sensitivity profiles and disease-free survival /overall survival are analysed using standard statistical methods.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gene expression profiles of childhood leukemia</measure>
    <time_frame>Baseline</time_frame>
    <description>Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug sensitivity profiles</measure>
    <time_frame>Baseline</time_frame>
    <description>Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Antibody efficacy for treatment of childhood leukemia</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Childhood Leukemia</condition>
  <arm_group>
    <arm_group_label>Childhood Leukemia</arm_group_label>
    <description>Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>RNA-seq</intervention_name>
    <description>Gene expression and fusion transcripts analysis</description>
    <arm_group_label>Childhood Leukemia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>whole exon sequencing</intervention_name>
    <description>Genetic alternation analysis</description>
    <arm_group_label>Childhood Leukemia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cytogenetics test</intervention_name>
    <description>Remission and relapse are monitored by cytogenetic analyses.</description>
    <arm_group_label>Childhood Leukemia</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood or bone marraw&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children suspected or diagnosed with leukemia at presentation will be recruited for the&#xD;
        study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        List of inclusion criteria:&#xD;
&#xD;
          1. acute lymphoblastic leukemia (ALL) or&#xD;
&#xD;
          2. acute myeloid leukemia (AML) or&#xD;
&#xD;
        3 .mixed phenotype acute leukemia (MPAL) or&#xD;
&#xD;
        4. juvenile myelomonocytic leukemia (JMML) or&#xD;
&#xD;
        5. myelodysplastic syndromes (MDS) or&#xD;
&#xD;
        6. normal bone marrow donor&#xD;
&#xD;
        List of exclusion criteria:&#xD;
&#xD;
          1. This study will not recruit subjects who are unable to understand English or Chinese.&#xD;
&#xD;
          2. Patient or parent refusal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kam Tong Leung, Ph. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kathy Chan, Ph. D.</last_name>
    <phone>852-35052858</phone>
    <email>kathyyychan@cuhk.edu.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kam Tong Leung, Ph. D.</last_name>
    <phone>852-35133176</phone>
    <email>ktleung@cuhk.edu.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hong Kong Children Hospital</name>
      <address>
        <city>Hong Kong</city>
        <state>Hksar</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kam Tong LEUNG, Ph. D.</last_name>
      <phone>852-35133176</phone>
      <email>ktleung@cuhk.edu.hk</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Kathy Chan</investigator_full_name>
    <investigator_title>Scientific Officer</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478006
org study id: HKCH-REC-2020-012
nct id: NCT04478006
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Genetic alterations of childhood leukemia
time frame: Baseline
description: Association of mutation data with drug sensitivity profiles and disease-free survival /overall survival are analysed using standard statistical methods.
measure: Gene expression profiles of childhood leukemia
time frame: Baseline
description: Global transcriptome and fusion transcripts of leukemic blasts are identified by RNA-sequencing.
measure: Drug sensitivity profiles
time frame: Baseline
description: Drug sensitivity results of individual patient blasts-derived ex vivo culture are presented as IC50 and AUC values.
measure: Antibody efficacy for treatment of childhood leukemia
time frame: Up to 1 year
description: 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.
arm group label: Childhood Leukemia
description: Peripheral blood and bone marrow samples are collected for genetic analysis, invitro drug sensitivity test and animal experiment.
intervention type: Genetic
intervention name: RNA-seq
description: Gene expression and fusion transcripts analysis
arm group label: Childhood Leukemia
intervention type: Genetic
intervention name: whole exon sequencing
description: Genetic alternation analysis
arm group label: Childhood Leukemia
intervention type: Other
intervention name: Cytogenetics test
description: Remission and relapse are monitored by cytogenetic analyses.
arm group label: Childhood Leukemia
Peripheral blood or bone marraw
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kam Tong Leung, Ph. D.
role: Principal Investigator
affiliation: Chinese University of Hong Kong
last name: Kathy Chan, Ph. D.
phone: 852-35052858
email: kathyyychan@cuhk.edu.hk
last name: Kam Tong Leung, Ph. D.
phone: 852-35133176
email: ktleung@cuhk.edu.hk
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Kathy Chan
investigator title: Scientific Officer
mesh term: Leukemia