<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/NCT02227641</url>
  </required_header>
  <id_info>
    <org_study_id>AIT-MULTIVIR-01</org_study_id>
    <secondary_id>2012-004240-30</secondary_id>
    <nct_id>NCT02227641</nct_id>
  </id_info>
  <brief_title>Preventative/Preemptive Adoptive Transfer of Peptide Stimulated CMV/EBV Specific T-cells in Patients After Allogeneic Stem Cell Transplantation</brief_title>
  <official_title>Prospective, Open, Randomized, Two-arm, Controlled, Multicenter Clinical Phase I/IIa Trial to Evaluate the Safety and Efficacy of Adoptive Immunotherapy With Allogeneic CMV/EBV Specific, Peptide Stimulated T-cells (CD3+) for Prevention or Preemptive Therapy of Reactivation of CMV and/or EBV in Patients After Allogeneic, HLA Identical Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Erlangen-Nürnberg Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Regensburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Augsburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>BayImmuNet Bavarian Immunotherapy Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>German Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Erlangen-Nürnberg Medical School</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses&#xD;
      such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening&#xD;
      complication requiring antiviral treatment. The underlying problem is a severe suppression of&#xD;
      the donors immune system after transplantation into the patient. Herpesviruses such as CMV&#xD;
      and EBV persist after primary infection life long in the host and therefore require constant&#xD;
      immunological control. This control is largely provided by the T-cell compartment of the&#xD;
      immune system. After allogeneic stem cell transplantation the T-cell compartment requires a&#xD;
      long time for its reconstitution since only a small fraction of the donor T-cells are&#xD;
      transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell&#xD;
      control.&#xD;
&#xD;
      This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific&#xD;
      T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a&#xD;
      phase I study to demonstrate that these in vitro generated T-cells can be applied safely in&#xD;
      this patient population. The study also aims at demonstrating the efficacy of CMV/EBV&#xD;
      specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis&#xD;
      is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host&#xD;
      disease and that they successfully prevent reactivation of CMV and EBV after adoptive&#xD;
      transfer in patients after allogeneic stem cell transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">October 2016</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>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicity of adoptive transfer of CMV/EBV specific T-cells</measure>
    <time_frame>1-28 days after adoptive T-cell transfer</time_frame>
    <description>Assessment of acute transfusion toxicity within 24 hours after adoptive T-cell transfer.&#xD;
Assessment of the development of acute transfusion associated acute graft versus host disease (GvHD) within 28 days after adoptive T-cell transfer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation</measure>
    <time_frame>During observation period until day 204 post transplantation</time_frame>
    <description>Incidence of reactivation of CMV and/or EBV during the observation period assessed by virus specific PCR of peripheral blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy</measure>
    <time_frame>During observation period until day 204 post transplantation</time_frame>
    <description>Cumulative dose of Ganciclovir, Valganciclovir, Foscarnet, Cidofovir</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab</measure>
    <time_frame>During observation period until day 204 post transplantation</time_frame>
    <description>Cumulative dose of Rituximab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution</measure>
    <time_frame>During observation period until day 204 post transplantation</time_frame>
    <description>Immunomonitoring of peripheral blood by flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Patients Undergoing Allogeneic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Adoptive transfer of CMV/EBV specific T-cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Repetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Observation only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CMV/EBV specific T-cell</intervention_name>
    <description>Peptide stimulated allogeneic T-cells with dual specificity for CMV and EBV</description>
    <arm_group_label>Adoptive transfer of CMV/EBV specific T-cells</arm_group_label>
    <other_name>T cell</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Indication for allogeneic stem cell transplantation&#xD;
&#xD;
          -  HLA identical donor, related or unrelated, 10/10 match&#xD;
&#xD;
          -  Stem cell source: G-SCF mobilized peripheral blood stem cells&#xD;
&#xD;
          -  Presence of at least one HLA allele: A0101, A0201, B0702, B0801, B3501, C0702&#xD;
&#xD;
          -  Positive EBV serology of the donor&#xD;
&#xD;
          -  Positive CMV serology of the donor&#xD;
&#xD;
          -  Adequate contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Donor CMV seronegative&#xD;
&#xD;
          -  Donor EBV seronegative&#xD;
&#xD;
          -  Stem cell source: bone marrow or cord blood&#xD;
&#xD;
          -  Alemtuzumab for conditioning&#xD;
&#xD;
          -  Sorror Score &gt;3&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Armin H Gerbitz, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bernd Spriewald, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Erlangen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anita Kremer, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Erlangen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Katja San Niccolo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Erlangen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical Center Augsburg</name>
      <address>
        <city>Augsburg</city>
        <zip>86156</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité University Hospital Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitiy Hospital Erlangen</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Munich LMU</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Regensburg</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.medizin5.uk-erlangen.de/</url>
    <description>Dept. of Medicine 5, Hematology/Oncology, University of Erlangen</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>December 10, 2020</last_update_submitted>
  <last_update_submitted_qc>December 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CMV</keyword>
  <keyword>Cytomegalovirus</keyword>
  <keyword>EBV</keyword>
  <keyword>Epstein Barr Virus</keyword>
  <keyword>virus</keyword>
  <keyword>T cell</keyword>
  <keyword>adoptive transfer</keyword>
  <keyword>transplantation</keyword>
  <keyword>allogeneic</keyword>
  <!-- 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/NCT02227641
org study id: AIT-MULTIVIR-01
secondary id: 2012-004240-30
nct id: NCT02227641
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses
      such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening
      complication requiring antiviral treatment. The underlying problem is a severe suppression of
      the donors immune system after transplantation into the patient. Herpesviruses such as CMV
      and EBV persist after primary infection life long in the host and therefore require constant
      immunological control. This control is largely provided by the T-cell compartment of the
      immune system. After allogeneic stem cell transplantation the T-cell compartment requires a
      long time for its reconstitution since only a small fraction of the donor T-cells are
      transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell
      control.

      This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific
      T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a
      phase I study to demonstrate that these in vitro generated T-cells can be applied safely in
      this patient population. The study also aims at demonstrating the efficacy of CMV/EBV
      specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis
      is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host
      disease and that they successfully prevent reactivation of CMV and EBV after adoptive
      transfer in patients after allogeneic stem cell transplantation.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Toxicity of adoptive transfer of CMV/EBV specific T-cells
time frame: 1-28 days after adoptive T-cell transfer
description: Assessment of acute transfusion toxicity within 24 hours after adoptive T-cell transfer.
Assessment of the development of acute transfusion associated acute graft versus host disease (GvHD) within 28 days after adoptive T-cell transfer
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation
time frame: During observation period until day 204 post transplantation
description: Incidence of reactivation of CMV and/or EBV during the observation period assessed by virus specific PCR of peripheral blood.
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy
time frame: During observation period until day 204 post transplantation
description: Cumulative dose of Ganciclovir, Valganciclovir, Foscarnet, Cidofovir
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab
time frame: During observation period until day 204 post transplantation
description: Cumulative dose of Rituximab.
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution
time frame: During observation period until day 204 post transplantation
description: Immunomonitoring of peripheral blood by flow cytometry.
arm group label: Adoptive transfer of CMV/EBV specific T-cells
arm group type: Experimental
description: Repetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation.
arm group label: Control
arm group type: No Intervention
description: Observation only.
intervention type: Biological
intervention name: CMV/EBV specific T-cell
description: Peptide stimulated allogeneic T-cells with dual specificity for CMV and EBV
arm group label: Adoptive transfer of CMV/EBV specific T-cells
other name: T cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Armin H Gerbitz, MD, PhD
role: Study Director
affiliation: Charite University, Berlin, Germany
last name: Bernd Spriewald, MD, PhD
role: Principal Investigator
affiliation: University Hospital Erlangen
last name: Anita Kremer, MD,PhD
role: Principal Investigator
affiliation: University Hospital Erlangen
last name: Katja San Niccolo, MD
role: Principal Investigator
affiliation: University Hospital Erlangen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
url: http://www.medizin5.uk-erlangen.de/
description: Dept. of Medicine 5, Hematology/Oncology, University of Erlangen
responsible party type: Sponsor