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/NCT06021210</url>
    </required_header>
    <id_info>
      <org_study_id>mNGS+LMV</org_study_id>
      <nct_id>NCT06021210</nct_id>
    </id_info>
    <brief_title>Letermovir for the Prevention of CMV Infection in HSCT Recipients Based on the Outcome of mNGS</brief_title>
    <official_title>Letermovir for the Prevention of Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients Based on the Outcome of Metagenomic Next-Generation Sequencing: a Phase 2, Open Label, Single-Arm Clinical Trial.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The First Affiliated Hospital of Soochow University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The First Affiliated Hospital of Soochow University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Letermovir for the Prevention of CMV Infection in HSCT Recipients Based on the Outcome of&#xD;
        mNGS&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used as the sole&#xD;
        curative treatment for malignant hematological diseases. However, the chances of contracting&#xD;
        various pathogenic bacterial infections significantly increase after transplantation, with&#xD;
        cytomegalovirus (CMV) infection being the most prevalent [1]. The propotion of&#xD;
        CMV-seropositive people ranges from 30% to 97%. After a previous infection, CMV can remain&#xD;
        latent in the patient's body and reactivate when the immune function is low, which is the&#xD;
        primary cause of CMV infection in allo-HSCT patients, leading to CMV viremia and CMV disease.&#xD;
        If CMV viremia progresses to CMV disease, it can invade various organs such as the lungs,&#xD;
        digestive tract, retina, and brain, with CMV pneumonia having a mortality rate of over 80%&#xD;
        [2]. After allo-HSCT, the incidence of CMV disease ranges from 60% to 70%, depending on the&#xD;
        serological status of the donor and recipient [3-4].&#xD;
  &#xD;
        In the past, antiviral drugs including ganciclovir, foscarnet, cidofovir, and&#xD;
        valganciclovir/valacyclovir were commonly used to treat or prevent CMV infections in clinical&#xD;
        practice. These drugs target on viral DNA polymerase, which in turn inhibits the replication&#xD;
        of CMV DNA. However, these drugs have serious side effects, such as bone marrow suppression&#xD;
        and severe nephrotoxicity, which limit their clinical application.&#xD;
  &#xD;
        Letermovir is the world's first and only new drug approved for the prevention of CMV&#xD;
        infection. In 2017, it was approved by the U.S. Food and Drug Administration (FDA) for the&#xD;
        prevention of CMV infection and disease in CMV-seropositive adult recipients (R+) of&#xD;
        allogeneic hematopoietic stem cell transplantation (allo-HSCT). It was approved in China on&#xD;
        December 31, 2021. Letermovir targets on the CMV DNA terminase complex consisting of pUL51,&#xD;
        pUL56, and pUL89, which affects the formation of appropriate unit-length genomes and&#xD;
        interferes with the maturation of virus particles. Therefore, due to its unique&#xD;
        pharmacological mechanism, Letermovir does not affect the normal function of human cells,&#xD;
        which can avoid the common side effects of other anti-CMV drugs, and it does not develop&#xD;
        cross-resistance with other antiviral drugs. Letermovir does not affect the incidence and&#xD;
        timing of hematopoietic stem cell implantation and is an effective and safe first-line drug&#xD;
        for the prevention of CMV infection and disease after allo-HSCT. It is recommended for&#xD;
        CMV-seropositive adult allo-HSCT recipients to use Letermovir for CMV prophylaxis from day 0&#xD;
        after transplantation, no later than day 28 after transplantation (can be used before&#xD;
        implantation), and continue until day 100 after transplantation.&#xD;
  &#xD;
        The mNGS (metagenomic next-generation sequencing) detection method is a new high-throughput&#xD;
        sequencing method for analyzing the microbiome in clinical samples, independent of&#xD;
        traditional microbial cultivation. It involves extracting nucleic acid sequences from the&#xD;
        samples, constructing sequencing libraries, sequencing the nucleic acid sequences in the&#xD;
        sample, and comparing them to a microbial-specific database for analysis. Through intelligent&#xD;
        algorithms, it identifies the species information of suspected pathogenic microorganisms with&#xD;
        high sensitivity. The mNGS method can detect potential CMV infection in patients before&#xD;
        having positive outcomes in qPCR detection of CMV-DNA, and has been used clinically.&#xD;
  &#xD;
        This study will evaluate the efficacy and safety of using letermovir to prevent CMV&#xD;
        reactivation for high-risk patients with pre-existing CMV viremia based on the mNGS detection&#xD;
        technology before HSCT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 7, 2022</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of clinically significant CMV infection with letermovir prevention after HSCT Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>The diagnosis of CMV infection is based on CMV-DNA detection of qPCR.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidences of CMV reactivation</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>The cumulative incidences of CMV reactivation after transplantion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Acute and/or chronic graft versus host disease(a/cGVHD)</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of transplantation Complications after transplantation</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>Incidence of transplantation Complications such as mucositis, hepatic veno-occlusive disease(SOS), thrombotic microangiopathy(TMA), interstitial pneumonia, hemorrhagic cystitis, infections etc.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of CMV-related disease mortality</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>The Incidence of CMV-related disease mortality after transplantation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of all-cause mortality and non-relapse mortality</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>The Incidence of all-cause mortality and non-relapse mortality after transplantion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Leukemia-free survival(LFS)</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>Leukemia-free survival(LFS) is defined as the time from enrollment to relapse of primary disease or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival(OS)</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>Overall survival(OS) is defined as the time from transplantation to death resulting from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GVHD-free and relapse-free survival(GRFS)</measure>
      <time_frame>Time from registration to event, max 24 weeks</time_frame>
      <description>GRFS is defined as the time from graft infusion to the onset of grades 3 to 4 aGVHD, moderate to severe cGVHD, or relapse/disease progression/death.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>CMV Infection</condition>
    <condition>Hematopoietic Stem Cell Transplantation</condition>
    <arm_group>
      <arm_group_label>mNGS detection before stem cell transplantation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Using letermovir to prevent CMV reactivation for high-risk patients with pre-existing CMV viremia based on the mNGS detection technology before HSCT</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Letermovir Pill</intervention_name>
      <description>Letermovir is the world's first and only new drug approved for the prevention of CMV infection. In 2017, it was approved by the U.S. Food and Drug Administration (FDA) for the prevention of CMV infection and disease in CMV-seropositive adult recipients (R+) of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It was approved in China on December 31, 2021.</description>
      <arm_group_label>mNGS detection before stem cell transplantation</arm_group_label>
      <other_name>Letermovir Tablets</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  HSCT candidate who has decided to primary transplant and is willing to participate in&#xD;
               the study.&#xD;
  &#xD;
            -  HSCT candidate undergo mNGS detection before transplantation.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients below 14 years ago or above 65 years ago.&#xD;
  &#xD;
            -  Patients having active infection at the time of letermovir initiation.&#xD;
  &#xD;
            -  Patient recruited in a clinical study on an anti-CMV trial, or took similar anti-CMV&#xD;
               drugs previously.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Xiaowen Tang, PhD</last_name>
      <role>Study Chair</role>
      <affiliation>The First Affiliated Hospital of Soochow University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xiaowen Tang, PhD</last_name>
      <phone>67781525</phone>
      <email>xwtang1020@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Depei Wu, PhD</last_name>
      <phone>67781525</phone>
      <email>drwudepei@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>The First Affiliated Hospital of Soochow University</name>
        <address>
          <city>Suzhou</city>
          <state>Jiangsu</state>
          <zip>215006</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Xiaowen Tang, PhD</last_name>
        <phone>67781525</phone>
        <email>xwtang1020@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 26, 2023</last_update_submitted>
    <last_update_submitted_qc>August 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The First Affiliated Hospital of Soochow University</investigator_affiliation>
      <investigator_full_name>Xiaowen Tang</investigator_full_name>
      <investigator_title>The First Affiliated Hospital of Soochow University</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infections</mesh_term>
      <mesh_term>Communicable Diseases</mesh_term>
      <mesh_term>Cytomegalovirus Infections</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Letermovir</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06021210
  org study id: mNGS+LMV
  nct id: NCT06021210
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Letermovir for the Prevention of CMV Infection in HSCT Recipients Based on the Outcome of
        mNGS
  Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used as the sole
        curative treatment for malignant hematological diseases. However, the chances of contracting
        various pathogenic bacterial infections significantly increase after transplantation, with
        cytomegalovirus (CMV) infection being the most prevalent [1]. The propotion of
        CMV-seropositive people ranges from 30% to 97%. After a previous infection, CMV can remain
        latent in the patient's body and reactivate when the immune function is low, which is the
        primary cause of CMV infection in allo-HSCT patients, leading to CMV viremia and CMV disease.
        If CMV viremia progresses to CMV disease, it can invade various organs such as the lungs,
        digestive tract, retina, and brain, with CMV pneumonia having a mortality rate of over 80%
        [2]. After allo-HSCT, the incidence of CMV disease ranges from 60% to 70%, depending on the
        serological status of the donor and recipient [3-4].
  
        In the past, antiviral drugs including ganciclovir, foscarnet, cidofovir, and
        valganciclovir/valacyclovir were commonly used to treat or prevent CMV infections in clinical
        practice. These drugs target on viral DNA polymerase, which in turn inhibits the replication
        of CMV DNA. However, these drugs have serious side effects, such as bone marrow suppression
        and severe nephrotoxicity, which limit their clinical application.
  
        Letermovir is the world's first and only new drug approved for the prevention of CMV
        infection. In 2017, it was approved by the U.S. Food and Drug Administration (FDA) for the
        prevention of CMV infection and disease in CMV-seropositive adult recipients (R+) of
        allogeneic hematopoietic stem cell transplantation (allo-HSCT). It was approved in China on
        December 31, 2021. Letermovir targets on the CMV DNA terminase complex consisting of pUL51,
        pUL56, and pUL89, which affects the formation of appropriate unit-length genomes and
        interferes with the maturation of virus particles. Therefore, due to its unique
        pharmacological mechanism, Letermovir does not affect the normal function of human cells,
        which can avoid the common side effects of other anti-CMV drugs, and it does not develop
        cross-resistance with other antiviral drugs. Letermovir does not affect the incidence and
        timing of hematopoietic stem cell implantation and is an effective and safe first-line drug
        for the prevention of CMV infection and disease after allo-HSCT. It is recommended for
        CMV-seropositive adult allo-HSCT recipients to use Letermovir for CMV prophylaxis from day 0
        after transplantation, no later than day 28 after transplantation (can be used before
        implantation), and continue until day 100 after transplantation.
  
        The mNGS (metagenomic next-generation sequencing) detection method is a new high-throughput
        sequencing method for analyzing the microbiome in clinical samples, independent of
        traditional microbial cultivation. It involves extracting nucleic acid sequences from the
        samples, constructing sequencing libraries, sequencing the nucleic acid sequences in the
        sample, and comparing them to a microbial-specific database for analysis. Through intelligent
        algorithms, it identifies the species information of suspected pathogenic microorganisms with
        high sensitivity. The mNGS method can detect potential CMV infection in patients before
        having positive outcomes in qPCR detection of CMV-DNA, and has been used clinically.
  
        This study will evaluate the efficacy and safety of using letermovir to prevent CMV
        reactivation for high-risk patients with pre-existing CMV viremia based on the mNGS detection
        technology before HSCT.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of clinically significant CMV infection with letermovir prevention after HSCT Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease
  time frame: Time from registration to event, max 24 weeks
  description: The diagnosis of CMV infection is based on CMV-DNA detection of qPCR.
  measure: Cumulative incidences of CMV reactivation
  time frame: Time from registration to event, max 24 weeks
  description: The cumulative incidences of CMV reactivation after transplantion.
  measure: Incidence of Acute and/or chronic graft versus host disease(a/cGVHD)
  time frame: Time from registration to event, max 24 weeks
  description: The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.
  measure: Incidence of transplantation Complications after transplantation
  time frame: Time from registration to event, max 24 weeks
  description: Incidence of transplantation Complications such as mucositis, hepatic veno-occlusive disease(SOS), thrombotic microangiopathy(TMA), interstitial pneumonia, hemorrhagic cystitis, infections etc.
  measure: Incidence of CMV-related disease mortality
  time frame: Time from registration to event, max 24 weeks
  description: The Incidence of CMV-related disease mortality after transplantation.
  measure: Incidence of all-cause mortality and non-relapse mortality
  time frame: Time from registration to event, max 24 weeks
  description: The Incidence of all-cause mortality and non-relapse mortality after transplantion.
  measure: Leukemia-free survival(LFS)
  time frame: Time from registration to event, max 24 weeks
  description: Leukemia-free survival(LFS) is defined as the time from enrollment to relapse of primary disease or death from any cause.
  measure: Overall survival(OS)
  time frame: Time from registration to event, max 24 weeks
  description: Overall survival(OS) is defined as the time from transplantation to death resulting from any cause.
  measure: GVHD-free and relapse-free survival(GRFS)
  time frame: Time from registration to event, max 24 weeks
  description: GRFS is defined as the time from graft infusion to the onset of grades 3 to 4 aGVHD, moderate to severe cGVHD, or relapse/disease progression/death.
  arm group label: mNGS detection before stem cell transplantation
  arm group type: Experimental
  description: Using letermovir to prevent CMV reactivation for high-risk patients with pre-existing CMV viremia based on the mNGS detection technology before HSCT
  intervention type: Drug
  intervention name: Letermovir Pill
  description: Letermovir is the world's first and only new drug approved for the prevention of CMV infection. In 2017, it was approved by the U.S. Food and Drug Administration (FDA) for the prevention of CMV infection and disease in CMV-seropositive adult recipients (R+) of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It was approved in China on December 31, 2021.
  arm group label: mNGS detection before stem cell transplantation
  other name: Letermovir Tablets
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Xiaowen Tang, PhD
  role: Study Chair
  affiliation: The First Affiliated Hospital of Soochow University
  last name: Xiaowen Tang, PhD
  phone: 67781525
  email: xwtang1020@163.com
  last name: Depei Wu, PhD
  phone: 67781525
  email: drwudepei@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: The First Affiliated Hospital of Soochow University
  investigator full name: Xiaowen Tang
  investigator title: The First Affiliated Hospital of Soochow University
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Cytomegalovirus Infections
  mesh term: Letermovir
  sharing ipd: No