<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/NCT02985775</url>
  </required_header>
  <id_info>
    <org_study_id>2016PHB153</org_study_id>
    <nct_id>NCT02985775</nct_id>
  </id_info>
  <brief_title>Preemptive Therapy With CMV-specific T Cells Infusion to Prevent Refractory CMV Infection Post Transplantation</brief_title>
  <official_title>Evaluate the Safety and Efficacy of Preemptive Adoptive CMV-specific T Cells Infusion for Prevention of Refractory CMV Infection in Patients After Haploidentical Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University People's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cytomegalovirus (CMV) infections remain an important cause of morbidity and mortality in&#xD;
      allogeneic hematopoietic cell transplant (HSCT) recipients, especially in patients received&#xD;
      haploidentical transplantation. During the past decades, prophylactic or preemptive treatment&#xD;
      with antiviral drugs has significantly reduce the incidence of early-onset CMV infection.&#xD;
      Unfortunately, prolonged antiviral treatment is associated with substantial toxicity and may&#xD;
      delay recovery of virus specific immune responses, resulting in an increasing of late-onset&#xD;
      CMV disease.&#xD;
&#xD;
      To date, adoptive immunotherapies have been developed as treatment alternatives to antiviral&#xD;
      agents for CMV infection after HSCT. Studies have demonstrated that prophylactic or&#xD;
      preemptive therapy with donor CMV-specific T cells can restore antiviral immunity and clear&#xD;
      CMV viremia after transplantation. In this prospective clinical phase I/II trial, we propose&#xD;
      to reconstitute antiviral immunity against CMV by preemptive transfer of CMV-specific T cells&#xD;
      at an early time point after allogeneic stem cell transplantation. We also propose to&#xD;
      demonstrate whether protect against CMV is associated with recovery of CMV-specific T cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute lymphoblastic leukemia (ALL) patients enrolled into this clinical trial are standard&#xD;
      risk patients diagnosed with acute leukemia or myelodysplastic syndrome (MDS) and received&#xD;
      haploidentical blood and marrow transplantation. When patients develop acute graft versus&#xD;
      host disease (aGVHD), CMVpp65-specific T cells will be generated and transferred to the aGVHD&#xD;
      controlled patients(patients who do not develop aGVHD are at low risk of refractory CMV&#xD;
      infection, and are not include in treated group). Physical exams and blood tests will be&#xD;
      performed -2w, -0d before and +1d, +2w, +4w, +8w, +12w, +24w after adoptive CMV-CTL&#xD;
      transfusion. The end points were safety and clinical and immunologic response. Following time&#xD;
      is 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">March 2018</primary_completion_date>
  <phase>Phase 1/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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation</measure>
    <time_frame>6 months</time_frame>
    <description>Virologic efficacy defined as reduction of refractory CMV infection during 6 months after transplantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after adoptive transfer of CMV-specific T-cells</measure>
    <time_frame>6 months</time_frame>
    <description>Patients were closely monitored for acute infusion-related toxicities during the first 2 to 4 hours following T-cell transfer and later on for acute and chronic GVHD during the whole observation period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation</measure>
    <time_frame>6 months</time_frame>
    <description>Immunologic efficacy defined as in vivo reconstitution of CMV-specific antiviral immunity after adoptive transfer of CMV-CTLs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction complications associated with CMV infection</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction relapse rate of the primary disease</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Increase overall survival</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Increase disease-free survival</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>CMV Infection</condition>
  <arm_group>
    <arm_group_label>Donor-derived CMVpp65-specific T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention to be adminstered is about 1 million per kg CMVpp65-specific T cells infusion once acute GVHD ocurred post haploidentical transplantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Donor-derived CMVpp65-specific T cells</intervention_name>
    <description>About 1 million per kg CMVpp65-specific T cells will be infused once acute GVHD ocurred post haploidentical transplantation.</description>
    <arm_group_label>Donor-derived CMVpp65-specific T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary disease is leukemia or MDS.&#xD;
&#xD;
          2. Patients receive haploidentical stem cell transplantation.&#xD;
&#xD;
          3. Both patients and donors are CMV seropositive (IgG positive).&#xD;
&#xD;
          4. Subjects must be capable of, and willing to provide written informed consent to&#xD;
             participate in the study. Subjects unable to provide written informed consent by&#xD;
             themselves may be consented through their legal representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in another industry-sponsored clinical study where treatment for CMV is&#xD;
             already specified by the study protocol.&#xD;
&#xD;
          2. Patients received other adoptive immunotherapy such as donor lymphocyte infusion&#xD;
             (DLI), Epstein-Barr virus (EBV)-specific T cells and so on.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiao-jun Huang, MD,PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University People's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking University People's Hospital &amp; Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>March 9, 2020</last_update_submitted>
  <last_update_submitted_qc>March 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University People's Hospital</investigator_affiliation>
    <investigator_full_name>Xiaojun Huang,MD</investigator_full_name>
    <investigator_title>MD,PHD, Study Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>CMV-specific T cell</keyword>
  <keyword>haploidentical stem cell transplantation</keyword>
  <keyword>immunologic response</keyword>
  <keyword>acute GVHD</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02985775
org study id: 2016PHB153
nct id: NCT02985775
lead sponsor: 
has dmc: Yes
Cytomegalovirus (CMV) infections remain an important cause of morbidity and mortality in
      allogeneic hematopoietic cell transplant (HSCT) recipients, especially in patients received
      haploidentical transplantation. During the past decades, prophylactic or preemptive treatment
      with antiviral drugs has significantly reduce the incidence of early-onset CMV infection.
      Unfortunately, prolonged antiviral treatment is associated with substantial toxicity and may
      delay recovery of virus specific immune responses, resulting in an increasing of late-onset
      CMV disease.

      To date, adoptive immunotherapies have been developed as treatment alternatives to antiviral
      agents for CMV infection after HSCT. Studies have demonstrated that prophylactic or
      preemptive therapy with donor CMV-specific T cells can restore antiviral immunity and clear
      CMV viremia after transplantation. In this prospective clinical phase I/II trial, we propose
      to reconstitute antiviral immunity against CMV by preemptive transfer of CMV-specific T cells
      at an early time point after allogeneic stem cell transplantation. We also propose to
      demonstrate whether protect against CMV is associated with recovery of CMV-specific T cells.
Acute lymphoblastic leukemia (ALL) patients enrolled into this clinical trial are standard
      risk patients diagnosed with acute leukemia or myelodysplastic syndrome (MDS) and received
      haploidentical blood and marrow transplantation. When patients develop acute graft versus
      host disease (aGVHD), CMVpp65-specific T cells will be generated and transferred to the aGVHD
      controlled patients(patients who do not develop aGVHD are at low risk of refractory CMV
      infection, and are not include in treated group). Physical exams and blood tests will be
      performed -2w, -0d before and +1d, +2w, +4w, +8w, +12w, +24w after adoptive CMV-CTL
      transfusion. The end points were safety and clinical and immunologic response. Following time
      is 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation
time frame: 6 months
description: Virologic efficacy defined as reduction of refractory CMV infection during 6 months after transplantation
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after adoptive transfer of CMV-specific T-cells
time frame: 6 months
description: Patients were closely monitored for acute infusion-related toxicities during the first 2 to 4 hours following T-cell transfer and later on for acute and chronic GVHD during the whole observation period.
measure: Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation
time frame: 6 months
description: Immunologic efficacy defined as in vivo reconstitution of CMV-specific antiviral immunity after adoptive transfer of CMV-CTLs
measure: Reduction complications associated with CMV infection
time frame: 6 months
measure: Reduction relapse rate of the primary disease
time frame: 6 months
measure: Increase overall survival
time frame: 6 months
measure: Increase disease-free survival
time frame: 6 months
arm group label: Donor-derived CMVpp65-specific T cells
arm group type: Experimental
description: Intervention to be adminstered is about 1 million per kg CMVpp65-specific T cells infusion once acute GVHD ocurred post haploidentical transplantation.
intervention type: Biological
intervention name: Donor-derived CMVpp65-specific T cells
description: About 1 million per kg CMVpp65-specific T cells will be infused once acute GVHD ocurred post haploidentical transplantation.
arm group label: Donor-derived CMVpp65-specific T cells
criteria: 
gender: All
minimum age: 15 Years
maximum age: 65 Years
healthy volunteers: No
last name: Xiao-jun Huang, MD,PHD
role: Principal Investigator
affiliation: Peking University People's Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University People's Hospital
investigator full name: Xiaojun Huang,MD
investigator title: MD,PHD, Study Principal Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Cytomegalovirus Infections
sharing ipd: Undecided