<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/NCT03004261</url>
  </required_header>
  <id_info>
    <org_study_id>CMV-CTL-201609</org_study_id>
    <nct_id>NCT03004261</nct_id>
  </id_info>
  <brief_title>CMV-CTL for the Treatment of CMV Infection After HSCT</brief_title>
  <official_title>Cytomegalovirus Specific Cytotoxic T Lymphocyte for the Treatment of Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for&#xD;
      recipients of allogeneic hematopoietic stem cell transplantation(HSCT). we propose to study&#xD;
      the immunologic and virologic effects of donor derived CMV specific cytotoxic T lymphocyte&#xD;
      (CMV-CTL) given to transplant recipients&#xD;
&#xD;
      CMV antigen peptides will be used to induce the CMV antigen specific T lymphocytes derived&#xD;
      from donor peripheral blood mononuclear cells for a period of 18~21 days.The patients will&#xD;
      receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The&#xD;
      CMV-DNA level will be monitored weekly after transfusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allogeneic hematopoietic stem cell transplantation is widely used for the treatment of&#xD;
      hematological malignancies and bone marrow failure diseases. Human cytomegalovirus (CMV)&#xD;
      infection is a major cause of morbidity and mortality for recipients of allogeneic&#xD;
      hematopoietic stem cell transplantation(HSCT). Approximately half of the recipients would&#xD;
      develop CMV infection after transplant. Present treatment recommendation for CMV infection&#xD;
      including ganciclovir and foscarnet. However, these medications have many side effects, the&#xD;
      most serious is myelosuppression and renal injury, moreover, many patients do not response to&#xD;
      these medications. Considering the risk associated with persistent infection and the&#xD;
      potential for CMV specific cytotoxic T lymphocyte (CMV-CTL) to restore immunity, we propose&#xD;
      to study the immunologic and virologic effects of donor derived CMV-CTL given to transplant&#xD;
      recipients, levels of CMV-CTL and CMV DNA will be measured from CTL recipients.&#xD;
&#xD;
      If the patient and their donor are eligible, we will take 80 ml of fresh blood from the donor&#xD;
      or 5 ml peripheral blood stem cell from the donor.The peripheral blood mononuclear cells will&#xD;
      be separated from peripheral blood or peripheral blood stem cell. CMV antigen peptides will&#xD;
      be used to induce the CMV-CTL for a period of 18~21 days.&#xD;
&#xD;
      The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The&#xD;
      patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 30&#xD;
      days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after&#xD;
      the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral&#xD;
      infection, then they may be eligible to receive one additional injection of CTLs. If the CMV&#xD;
      levels in the blood continue to rise after the dose of T cells then the patient will receive&#xD;
      treatment with Ganciclovir, Foscarnet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>Phase 4</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>30-day response rate</measure>
    <time_frame>from the date of CMV-CTL infusion to 30 days after the infusion</time_frame>
    <description>The percentage of patient whose serum CMV-DNA becomes negative in 30 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>1-year overall survival</measure>
    <time_frame>from the date of transplant to 1 year after transplant</time_frame>
    <description>The length of patients who are alive in 1 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>100-day incidence of acute GVHD</measure>
    <time_frame>from the date of transplant to 100 days after transplant</time_frame>
    <description>the incidence of acute GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year incidence of chronic GVHD</measure>
    <time_frame>from the date of transplant to 1 year after transplant</time_frame>
    <description>the incidence of chronic GVHD</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Cytomegalovirus Infections</condition>
  <condition>Hematological Disease</condition>
  <arm_group>
    <arm_group_label>CMV-CTL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>donor derived cytomegalovirus specific T lymphocytes</intervention_name>
    <description>donor derived cytomegalovirus specific T lymphocytes will be transfused to recipients of hematopoietic stem cell transplant when they are sero-positive for CMV-DNA.</description>
    <arm_group_label>CMV-CTL</arm_group_label>
    <other_name>cytomegalovirus specific T lymphocytes</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Foscarnet</intervention_name>
    <description>Foscarnet may be used for the treatment of CMV infection before and after the CMV-CTL infusion.</description>
    <arm_group_label>CMV-CTL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ganciclovir</intervention_name>
    <description>Ganciclovir may be used for the treatment of CMV infection before and after CMV-CTL infusion.</description>
    <arm_group_label>CMV-CTL</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any allogeneic stem cell transplant recipient ≥ 14 years of age and ≤ 60 years of age&#xD;
&#xD;
          -  Bilirubin/ SGOT/SGPT &lt; 5 × upper normal limits.&#xD;
&#xD;
          -  Creatinine &lt; 2 × upper normal limits.&#xD;
&#xD;
          -  Ejection fraction ≥ 50%, no severe arrhythmia.&#xD;
&#xD;
          -  Estimated life expectancy ≥ 6 months.&#xD;
&#xD;
          -  Patients' CMV-DNA ≥ 1000cp/ml in treatment group and being negative in prophylactic&#xD;
             group.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving prednisone ≥ 1mg/kg/d for the treatment of acute GVHD or mild,&#xD;
             severe chronic GVHD.&#xD;
&#xD;
          -  Recipient &lt; 14years of age&#xD;
&#xD;
          -  Donor is sero-positive in HBV/HCV/HIV or RPR.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Liping Wan, M.D.，Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiao Tong University Affiliated Shanghai General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shanghai Jiao Tong University Affilated Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Liping Wan</investigator_full_name>
    <investigator_title>Chief Physician</investigator_title>
  </responsible_party>
  <keyword>cytomegalovirus infection</keyword>
  <keyword>cytotoxic T lymphocyte</keyword>
  <keyword>hematopoietic stem cell transplantation</keyword>
  <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>
    <mesh_term>Hematologic Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ganciclovir</mesh_term>
    <mesh_term>Ganciclovir triphosphate</mesh_term>
    <mesh_term>Foscarnet</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03004261
org study id: CMV-CTL-201609
nct id: NCT03004261
lead sponsor: 
collaborator: 
has dmc: No
Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for
      recipients of allogeneic hematopoietic stem cell transplantation(HSCT). we propose to study
      the immunologic and virologic effects of donor derived CMV specific cytotoxic T lymphocyte
      (CMV-CTL) given to transplant recipients

      CMV antigen peptides will be used to induce the CMV antigen specific T lymphocytes derived
      from donor peripheral blood mononuclear cells for a period of 18~21 days.The patients will
      receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The
      CMV-DNA level will be monitored weekly after transfusion.
Allogeneic hematopoietic stem cell transplantation is widely used for the treatment of
      hematological malignancies and bone marrow failure diseases. Human cytomegalovirus (CMV)
      infection is a major cause of morbidity and mortality for recipients of allogeneic
      hematopoietic stem cell transplantation(HSCT). Approximately half of the recipients would
      develop CMV infection after transplant. Present treatment recommendation for CMV infection
      including ganciclovir and foscarnet. However, these medications have many side effects, the
      most serious is myelosuppression and renal injury, moreover, many patients do not response to
      these medications. Considering the risk associated with persistent infection and the
      potential for CMV specific cytotoxic T lymphocyte (CMV-CTL) to restore immunity, we propose
      to study the immunologic and virologic effects of donor derived CMV-CTL given to transplant
      recipients, levels of CMV-CTL and CMV DNA will be measured from CTL recipients.

      If the patient and their donor are eligible, we will take 80 ml of fresh blood from the donor
      or 5 ml peripheral blood stem cell from the donor.The peripheral blood mononuclear cells will
      be separated from peripheral blood or peripheral blood stem cell. CMV antigen peptides will
      be used to induce the CMV-CTL for a period of 18~21 days.

      The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The
      patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 30
      days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after
      the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral
      infection, then they may be eligible to receive one additional injection of CTLs. If the CMV
      levels in the blood continue to rise after the dose of T cells then the patient will receive
      treatment with Ganciclovir, Foscarnet.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 30-day response rate
time frame: from the date of CMV-CTL infusion to 30 days after the infusion
description: The percentage of patient whose serum CMV-DNA becomes negative in 30 days.
measure: 1-year overall survival
time frame: from the date of transplant to 1 year after transplant
description: The length of patients who are alive in 1 years.
measure: 100-day incidence of acute GVHD
time frame: from the date of transplant to 100 days after transplant
description: the incidence of acute GVHD
measure: 1-year incidence of chronic GVHD
time frame: from the date of transplant to 1 year after transplant
description: the incidence of chronic GVHD
arm group label: CMV-CTL
arm group type: Experimental
description: The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.
intervention type: Biological
intervention name: donor derived cytomegalovirus specific T lymphocytes
description: donor derived cytomegalovirus specific T lymphocytes will be transfused to recipients of hematopoietic stem cell transplant when they are sero-positive for CMV-DNA.
arm group label: CMV-CTL
other name: cytomegalovirus specific T lymphocytes
intervention type: Drug
intervention name: Foscarnet
description: Foscarnet may be used for the treatment of CMV infection before and after the CMV-CTL infusion.
arm group label: CMV-CTL
intervention type: Drug
intervention name: Ganciclovir
description: Ganciclovir may be used for the treatment of CMV infection before and after CMV-CTL infusion.
arm group label: CMV-CTL
criteria: 
gender: All
minimum age: 14 Years
maximum age: 60 Years
healthy volunteers: No
last name: Liping Wan, M.D.，Ph.D.
role: Principal Investigator
affiliation: Shanghai Jiao Tong University Affiliated Shanghai General Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
investigator full name: Liping Wan
investigator title: Chief Physician
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Cytomegalovirus Infections
mesh term: Hematologic Diseases
mesh term: Ganciclovir
mesh term: Ganciclovir triphosphate
mesh term: Foscarnet
sharing ipd: No