<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/NCT02982902</url>
  </required_header>
  <id_info>
    <org_study_id>CASE1Z16</org_study_id>
    <nct_id>NCT02982902</nct_id>
  </id_info>
  <brief_title>T Cell Therapy of Opportunistic Cytomegalovirus Infection</brief_title>
  <official_title>Antigen Specific Adoptive T Cell Therapy for Opportunistic Cytomegalovirus Infection Occurring After Stem Cell Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mari Dallas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Case Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if a specific type of cell-based immunotherapy,&#xD;
      using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to&#xD;
      treat infections by CMV.&#xD;
&#xD;
      Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the&#xD;
      blood of a donor and selecting the T-cells that can respond against a specific infectious&#xD;
      entity. These selected T-cells are then infused to the patient, to try to give the immune&#xD;
      system the ability to fight the infection. Adoptive T-cell therapy is experimental because it&#xD;
      is not approved by the Food and Drug Administration (FDA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to determine the feasibility of the treatment of&#xD;
      opportunistic cytomegalovirus (CMV) infections after hematopoietic stem cell transplant&#xD;
      (HSCT) with virus-specific, antigen-selected T-cells, selected using the CliniMACS prodigy&#xD;
      system.&#xD;
&#xD;
      Secondary Objective(s)&#xD;
&#xD;
        -  To describe the safety profile of the infusion of CMV- specific, antigen selected&#xD;
           T-cells.&#xD;
&#xD;
        -  To describe the toxicities related to infusion of CMV- specific, antigen selected&#xD;
           T-cells.&#xD;
&#xD;
        -  To describe the rate of eradication of opportunistic CMV infections after HSCT and and&#xD;
           treatment with CMV-specific, antigen-selected T-cells using the CliniMACS Prodigy&#xD;
           System.&#xD;
&#xD;
      This feasibility study will include a single treatment cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 27, 2020</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Early Phase 1</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 100 days after transplant</time_frame>
    <description>To determine the feasibility of the intervention, the study will record the incidence of adverse events, including graft versus host disease and other complications will be evaluated using binomial distribution theory and their 95% confidence intervals (CIs) will be also estimated using Wilson's method</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Eradication rate of opportunistic CMV infections</measure>
    <time_frame>Up to 100 days after transplant</time_frame>
    <description>The eradication rate will be the disappearance of opportunistic CMV infections with the use of CMV-specific, antigen-selected T cells using the CliniMACS Prodigy System over the total number CMV infections.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>response rate</measure>
    <time_frame>Up to 100 days after transplant</time_frame>
    <description>A response rate of 25% is considered unacceptable; and the anticipated response rate is approximately 55% for the study population using the cell therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Cytomegalovirus Infections</condition>
  <condition>Hematopoietic Stem Cell Transplant</condition>
  <condition>Opportunistic Infections</condition>
  <arm_group>
    <arm_group_label>CMV specific adoptive t-cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study involves a one-time infusion of the experimental CMV specific adoptive t-cells. After this infusion, patients will be followed for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CMV specific adoptive t-cells</intervention_name>
    <description>It is expected that the cell dose will be in the range of 10^3 - 10^5 virus - specific, antigen selected T cells per kg of recipient weight.</description>
    <arm_group_label>CMV specific adoptive t-cells</arm_group_label>
    <other_name>immunotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have received allogeneic hematopoietic stem cell transplant and be&#xD;
             greater than 30 days post-transplant at the time of registration&#xD;
&#xD;
          -  Patients must have documented opportunistic CMV infection, or reactivation; the&#xD;
             criteria include (both of the following criteria must be met)&#xD;
&#xD;
               -  Patients may have asymptomatic viremia (&gt;1000 copies/ml) OR presence of symptoms&#xD;
                  secondary to CMV infection, AND&#xD;
&#xD;
               -  Patients must have ONE OF THE NEXT FOUR CRITERIA:&#xD;
&#xD;
                    -  Absence of an improvement of viral load after ≥ 14 days of antiviral therapy&#xD;
                       with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log,&#xD;
                       i.e. 10-fold) or&#xD;
&#xD;
                    -  New, persistent and/or worsening CMV-related symptoms, signs and/or markers&#xD;
                       of end organ compromise while on antiviral therapy with ganciclovir,&#xD;
                       valganciclovir or foscarnet, or&#xD;
&#xD;
                    -  Have contraindications or experience adverse effects of antiviral therapy&#xD;
                       with ganciclovir, valganciclovir or foscarnet.&#xD;
&#xD;
                    -  Second recurrence of CMV viremia, CMV-related symptoms, signs and/or markers&#xD;
                       of end organ compromise.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (double barrier method of birth control or abstinence) 4 weeks prior to study entry,&#xD;
             for the duration of study participation and for 3 months after completing treatment.&#xD;
&#xD;
          -  Subjects must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document, or assent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding women are excluded from this study.&#xD;
&#xD;
          -  Patients with opportunistic viral infections other than CMV.&#xD;
&#xD;
          -  Patients with active, grade 2-4, acute graft vs. host disease (GVHD), chronic GVHD or&#xD;
             any condition requiring high doses of glucocorticosteroid (&gt;0.5 mg/kg/day prednisone&#xD;
             or its equivalent) as treatment&#xD;
&#xD;
          -  Treatment with antithymocyte globulin within 28 days of planned infusion of virus -&#xD;
             specific, antigen selected T cells.&#xD;
&#xD;
          -  Treatment with virus - specific T cells within 6 weeks (42 days) of planned infusion.&#xD;
&#xD;
        Donor eligibility&#xD;
&#xD;
          -  Related donor of T cells must be at least partially HLA compatible, matching with&#xD;
             recipient in at least 3/6 HLA loci (HLA-A, HLA-B, and HLA-DRB1 loci will be considered&#xD;
             for this).&#xD;
&#xD;
          -  Must have evidence of a serologic response (i.e. be seropositive) against CMV.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Must meet the criteria for donor selection defined in the Standard Operating&#xD;
             Procedures of University Hospitals Seidman Cancer Center Stem Cell Transplant Program&#xD;
&#xD;
          -  Must be capable of undergoing a single standard 2 blood volume leukapheresis or&#xD;
             donation of one unit of whole blood&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mari H Dallas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mari H Dallas, MD</last_name>
    <phone>1-800-641-2422</phone>
    <email>CTUReferral@UHhospitals.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106-5065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mari H Dallas, MD</last_name>
      <phone>800-641-2422</phone>
      <email>CTUReferral@UHhospitals.org</email>
    </contact>
    <investigator>
      <last_name>Mari H Dallas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>May 15, 2023</last_update_submitted>
  <last_update_submitted_qc>May 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Case Comprehensive Cancer Center</investigator_affiliation>
    <investigator_full_name>Mari Dallas</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>T-Cell Therapy</keyword>
  <keyword>Lymphoproliferative Disorder</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>Opportunistic Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02982902
org study id: CASE1Z16
nct id: NCT02982902
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine if a specific type of cell-based immunotherapy,
      using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to
      treat infections by CMV.

      Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the
      blood of a donor and selecting the T-cells that can respond against a specific infectious
      entity. These selected T-cells are then infused to the patient, to try to give the immune
      system the ability to fight the infection. Adoptive T-cell therapy is experimental because it
      is not approved by the Food and Drug Administration (FDA).
The primary objective of this study is to determine the feasibility of the treatment of
      opportunistic cytomegalovirus (CMV) infections after hematopoietic stem cell transplant
      (HSCT) with virus-specific, antigen-selected T-cells, selected using the CliniMACS prodigy
      system.

      Secondary Objective(s)

        -  To describe the safety profile of the infusion of CMV- specific, antigen selected
           T-cells.

        -  To describe the toxicities related to infusion of CMV- specific, antigen selected
           T-cells.

        -  To describe the rate of eradication of opportunistic CMV infections after HSCT and and
           treatment with CMV-specific, antigen-selected T-cells using the CliniMACS Prodigy
           System.

      This feasibility study will include a single treatment cohort.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Incidence of adverse events
time frame: Up to 100 days after transplant
description: To determine the feasibility of the intervention, the study will record the incidence of adverse events, including graft versus host disease and other complications will be evaluated using binomial distribution theory and their 95% confidence intervals (CIs) will be also estimated using Wilson's method
measure: Eradication rate of opportunistic CMV infections
time frame: Up to 100 days after transplant
description: The eradication rate will be the disappearance of opportunistic CMV infections with the use of CMV-specific, antigen-selected T cells using the CliniMACS Prodigy System over the total number CMV infections.
measure: response rate
time frame: Up to 100 days after transplant
description: A response rate of 25% is considered unacceptable; and the anticipated response rate is approximately 55% for the study population using the cell therapy.
arm group label: CMV specific adoptive t-cells
arm group type: Experimental
description: This study involves a one-time infusion of the experimental CMV specific adoptive t-cells. After this infusion, patients will be followed for 4 weeks.
intervention type: Biological
intervention name: CMV specific adoptive t-cells
description: It is expected that the cell dose will be in the range of 10^3 - 10^5 virus - specific, antigen selected T cells per kg of recipient weight.
arm group label: CMV specific adoptive t-cells
other name: immunotherapy
criteria: 
gender: All
minimum age: 3 Months
maximum age: N/A
healthy volunteers: No
last name: Mari H Dallas, MD
role: Principal Investigator
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
last name: Mari H Dallas, MD
phone: 1-800-641-2422
email: CTUReferral@UHhospitals.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Case Comprehensive Cancer Center
investigator full name: Mari Dallas
investigator title: Principal Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Cytomegalovirus Infections
mesh term: Opportunistic Infections
mesh term: Immunomodulating Agents