xml: <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/NCT05973032</url>
    </required_header>
    <id_info>
      <org_study_id>2023-IRB-0062</org_study_id>
      <nct_id>NCT05973032</nct_id>
    </id_info>
    <brief_title>MRD Detection by NGS in Pediatric B-ALL</brief_title>
    <official_title>Minimal Residual Disease Detection by Next-generation Sequencing of Different Immunoglobulin Gene Rearrangements in Pediatric B-ALL</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The Children's Hospital of Zhejiang University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The Children's Hospital of Zhejiang University School of Medicine</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>
        This retrospective analysis aims to investigate pediatric patients with B-cell acute&#xD;
        lymphoblastic leukemia who were detected for minimal residual disease (MRD) using&#xD;
        next-generation sequencing (NGS). The study will utilize second-generation sequencing&#xD;
        technology to analyze the rearrangement of the immunoglobulin heavy chain (IGH),&#xD;
        immunoglobulin kappa light chain (IGK), and immunoglobulin lambda light chain (IGL) genes in&#xD;
        these patients. Patients will be stratified based on NGS-MRD levels, and the relationship&#xD;
        between NGS-MRD and Event-Free Survival (EFS) will be evaluated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Design, Patients, and Procedures This was a prospective, single-center, observational&#xD;
        study conducted in children with ALL between November 2018 and June 2022. Children with newly&#xD;
        diagnosed B-ALL who undergone NGS of B-cell receptors at the Children's Hospital of Zhejiang&#xD;
        University School of Medicine were included in this study.&#xD;
  &#xD;
        The European Group for the Immunological Characterization of Leukemias (EGIL) criteria were&#xD;
        applied to diagnose and classify ALL in this study. All enrolled patients were treated&#xD;
        according to the ZJCH-ALL-2019 protocol detailed in the supplementary file. This protocol was&#xD;
        implemented in our center in September 2018 and subsequently extended to all of Zhejiang&#xD;
        Province in 2019. In this protocol, NGS-MRD was not used for patient risk stratification or&#xD;
        treatment allocation. For the detection of MRD, bone marrow (BM) aspiration for Ig NGS was&#xD;
        collected at diagnosis, the end of induction (EOI) at the 5th week from the initial&#xD;
        prednisone prephase, and the end of consolidation (EOC) at the 13th week which was before the&#xD;
        start of early intensification for low and intermediate risk patients, and was before the&#xD;
        start of the second course of consolidation for high-risk patients. NGS-MRD was sequentially&#xD;
        monitored every 2 to 3 months after consolidation until it was undetectable. In this study,&#xD;
        NGS-MRD refers to the quantitative value of MRD detected through NGS testing which was the&#xD;
        sum of IGH and light chain (IGK/IGL) levels. NGS detection during other timepoints, such as&#xD;
        the interim of induction and timepoints after NGS-MRD was negative, was not mandatory but&#xD;
        monitored as per parents' preference. The patients were followed up until August 30, 2022 and&#xD;
        the median follow-up time was 20.7 months.&#xD;
  &#xD;
        Statistical Analysis The association between categorical variables was tested using χ2 test,&#xD;
        the correlation between quantitative variables was measured using Pearson correlation and&#xD;
        tested using Student's t distribution, and ANOVA was used to compare quantitative variables.&#xD;
        Event-free survival (EFS) and overall survival (OS) curves were estimated using the&#xD;
        Kaplan-Meier method and compared according to the log rank test. Death during induction,&#xD;
        abandonment before complete remission, death in continuous complete remission, relapse, and&#xD;
        secondary malignancies were considered as events in the calculation of EFS probability. The&#xD;
        EFS time was calculated from the date of diagnosis to the last date of follow-up or the first&#xD;
        event. The OS was calculated from the date of diagnosis to death from any causes with&#xD;
        censoring the patients alive at the time of data analysis. The final date for follow-up was&#xD;
        August 30, 2022. Data visualization was performed using R package ggplot2 (Version 4.0.3) and&#xD;
        GraphPad Prism 9.0.0. Statistical analysis was performed on R (Version 4.0.3). A P value of&#xD;
        &lt;0.05 (2 tailed) was considered to be statistically significant.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">November 1, 2018</start_date>
    <completion_date type="Actual">August 31, 2022</completion_date>
    <primary_completion_date type="Actual">August 31, 2022</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>event-free survival</measure>
      <time_frame>Between November 2018 and June 2022</time_frame>
      <description>The EFS time was calculated from the date of diagnosis to the last date of follow-up or the first event.</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Actual">430</enrollment>
    <condition>Acute Lymphoblastic Leukemia, Pediatric, Next Generation Sequencing</condition>
    <arm_group>
      <arm_group_label>MRD positive and MRD negative groups</arm_group_label>
      <description>MRD postive: NGS-MRD&gt;=0.01% at the end of induction or &gt;=0.0001% at the end of consoidation.&#xD;
  MRD negative: NGS-MRD&lt;0.01% at the end of induction or &lt;0.0001% at the end of consoidation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>MRD</intervention_name>
      <description>Calculate the 3-year EFS based on the MRD status (MRD positive and negative groups)</description>
      <arm_group_label>MRD positive and MRD negative groups</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Children under the age of 18 years diagnosed with acute B-cell lymphoblastic leukemia&#xD;
          between 2018 and 2022.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Children with newly diagnosed B-ALL who undergone NGS of B-cell receptors&#xD;
  &#xD;
            -  Children older than 1 year receive treatment according to the ZJCH-ALL-2019 protocol,&#xD;
               while children younger than 1 year receive treatment according to the infant leukemia&#xD;
               protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  B-cell acute lymphoblastic leukemia (B-ALL) patients who have not undergone&#xD;
               high-throughput sequencing.&#xD;
  &#xD;
            -  Treated according to other protocols.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>The Children's Hospital of Zhejiang University School of Medicine</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310003</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The Children's Hospital of Zhejiang University School of Medicine</investigator_affiliation>
      <investigator_full_name>Xiaojun Xu</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05973032
  org study id: 2023-IRB-0062
  nct id: NCT05973032
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This retrospective analysis aims to investigate pediatric patients with B-cell acute
        lymphoblastic leukemia who were detected for minimal residual disease (MRD) using
        next-generation sequencing (NGS). The study will utilize second-generation sequencing
        technology to analyze the rearrangement of the immunoglobulin heavy chain (IGH),
        immunoglobulin kappa light chain (IGK), and immunoglobulin lambda light chain (IGL) genes in
        these patients. Patients will be stratified based on NGS-MRD levels, and the relationship
        between NGS-MRD and Event-Free Survival (EFS) will be evaluated.
  Study Design, Patients, and Procedures This was a prospective, single-center, observational
        study conducted in children with ALL between November 2018 and June 2022. Children with newly
        diagnosed B-ALL who undergone NGS of B-cell receptors at the Children's Hospital of Zhejiang
        University School of Medicine were included in this study.
  
        The European Group for the Immunological Characterization of Leukemias (EGIL) criteria were
        applied to diagnose and classify ALL in this study. All enrolled patients were treated
        according to the ZJCH-ALL-2019 protocol detailed in the supplementary file. This protocol was
        implemented in our center in September 2018 and subsequently extended to all of Zhejiang
        Province in 2019. In this protocol, NGS-MRD was not used for patient risk stratification or
        treatment allocation. For the detection of MRD, bone marrow (BM) aspiration for Ig NGS was
        collected at diagnosis, the end of induction (EOI) at the 5th week from the initial
        prednisone prephase, and the end of consolidation (EOC) at the 13th week which was before the
        start of early intensification for low and intermediate risk patients, and was before the
        start of the second course of consolidation for high-risk patients. NGS-MRD was sequentially
        monitored every 2 to 3 months after consolidation until it was undetectable. In this study,
        NGS-MRD refers to the quantitative value of MRD detected through NGS testing which was the
        sum of IGH and light chain (IGK/IGL) levels. NGS detection during other timepoints, such as
        the interim of induction and timepoints after NGS-MRD was negative, was not mandatory but
        monitored as per parents' preference. The patients were followed up until August 30, 2022 and
        the median follow-up time was 20.7 months.
  
        Statistical Analysis The association between categorical variables was tested using χ2 test,
        the correlation between quantitative variables was measured using Pearson correlation and
        tested using Student's t distribution, and ANOVA was used to compare quantitative variables.
        Event-free survival (EFS) and overall survival (OS) curves were estimated using the
        Kaplan-Meier method and compared according to the log rank test. Death during induction,
        abandonment before complete remission, death in continuous complete remission, relapse, and
        secondary malignancies were considered as events in the calculation of EFS probability. The
        EFS time was calculated from the date of diagnosis to the last date of follow-up or the first
        event. The OS was calculated from the date of diagnosis to death from any causes with
        censoring the patients alive at the time of data analysis. The final date for follow-up was
        August 30, 2022. Data visualization was performed using R package ggplot2 (Version 4.0.3) and
        GraphPad Prism 9.0.0. Statistical analysis was performed on R (Version 4.0.3). A P value of
        <0.05 (2 tailed) was considered to be statistically significant.
  observational model: Case-Only
  time perspective: Retrospective
  measure: event-free survival
  time frame: Between November 2018 and June 2022
  description: The EFS time was calculated from the date of diagnosis to the last date of follow-up or the first event.
  arm group label: MRD positive and MRD negative groups
  description: MRD postive: NGS-MRD>=0.01% at the end of induction or >=0.0001% at the end of consoidation.
  MRD negative: NGS-MRD<0.01% at the end of induction or <0.0001% at the end of consoidation.
  intervention type: Other
  intervention name: MRD
  description: Calculate the 3-year EFS based on the MRD status (MRD positive and negative groups)
  arm group label: MRD positive and MRD negative groups
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: 18 Years
  healthy volunteers: No
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: The Children's Hospital of Zhejiang University School of Medicine
  investigator full name: Xiaojun Xu
  investigator title: Principal investigator
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma