<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/NCT02210078</url>
  </required_header>
  <id_info>
    <org_study_id>2013-0657</org_study_id>
    <secondary_id>NCI-2014-01990</secondary_id>
    <secondary_id>2013-0657</secondary_id>
    <nct_id>NCT02210078</nct_id>
  </id_info>
  <brief_title>Donor Cytomegalovirus-Specific Cytotoxic T-Lymphocytes in Treating Patients With a Persistent Cytomegalovirus Infection</brief_title>
  <official_title>Most Closely HLA Matched Allogeneic CMV Specific Cytotoxic T-Lymphocytes (CTL) to Treat CMV Infection After Hemapoietic Stem Cell Transplantation (HSCT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well donor cytomegalovirus-specific cytotoxic T-lymphocytes&#xD;
      work in treating patients with a cytomegalovirus infection that has come back or has not&#xD;
      gotten better despite standard therapy. White blood cells from donors who have been exposed&#xD;
      to cytomegalovirus may be effective in treating patients with a cytomegalovirus infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To assess the efficacy, feasibility and safety of administering most closely human&#xD;
      leukocyte antigen (HLA)-matched cytomegalovirus (CMV) specific cytotoxic T-lymphocytes&#xD;
      (HMC-CTLs) generated by &quot;gamma-catch&quot; to mediate antiviral activity in hematopoietic stem&#xD;
      cell transplantation (HSCT) recipients with CMV infections.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To assess the persistency of the administered HMC-CTLs generated by &quot;gamma-catch&quot; and&#xD;
      their contribution immune reconstitution.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes intravenously&#xD;
      (IV). Patients with partial response, stable disease, or progressive disease may receive an&#xD;
      additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum&#xD;
      of 2 weeks from the first infusion.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically for 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 19, 2015</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 31, 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>Success, defined as R1 and R2 without treatment failure</measure>
    <time_frame>Up to 4 weeks after second CTL infusion</time_frame>
    <description>The best outcome is defined as R1 = in complete response (CR) for 4 consecutive weeks, starting at week 2, without the need for a second cytotoxic T-lymphocyte (CTL) infusion. The second best outcome is defined as R2 = not in CR at week 2, 3, or 4, but in CR or partial response (PR) 4 weeks after the second CTL infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival time</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival time</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft-versus-host disease</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary graft failure</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Cytomegaloviral Infection</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (allogeneic CMV-specific cytotoxic T-lymphocytes)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes IV. Patients with partial response, stable disease, or progressive disease may receive an additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum of 2 weeks from the first infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (allogeneic CMV-specific cytotoxic T-lymphocytes)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with or without a malignancy; and/or any type of autologous or allogeneic&#xD;
             HSCT; and/or patients who are immunocompromised with CMV infection will be included&#xD;
&#xD;
          -  Persistent CMV infection despite optimum anti-viral therapy&#xD;
&#xD;
               -  Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen&#xD;
                  from visceral sites (by culture or histology) or the detection of CMV by culture&#xD;
                  or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the&#xD;
                  presence of new or changing pulmonary infiltrates; OR&#xD;
&#xD;
               -  Failure of antiviral therapy: defined as the continued presence of&#xD;
                  deoxyribonucleic acid (DNA)emia (defined as &gt;= 137 copies/ml by polymerase chain&#xD;
                  reaction [PCR]) for at least 2 weeks of CMV antiviral therapy; OR&#xD;
&#xD;
                    -  Optimum therapy is defined as at least 14 days of therapy with ganciclovir,&#xD;
                       foscarnet, cidofovir, or valganciclovir for patients with disease or CMV&#xD;
                       viremia&#xD;
&#xD;
                    -  Relapse while on CMV antiviral therapy defined as recurrence of DNAemia&#xD;
                       while being on at least 2 weeks of antiviral therapy OR&#xD;
&#xD;
               -  Patients who cannot tolerate standard anti-viral therapy and cannot continue&#xD;
                  anti-viral treatment due to side effect profile will be eligible independent of&#xD;
                  anti-viral therapy duration&#xD;
&#xD;
          -  Clinical status at enrollment to allow tapering of steroids equal to or less than 0.5&#xD;
             mg/kg/day of prednisone&#xD;
&#xD;
          -  Patients with chronic graft-versus-host disease (GVHD) if on prednisone equal to or&#xD;
             less than 0.5 mg/kg and not receiving second-line GVHD treatments like pentostatin,&#xD;
             infliximab, etanercept, etc&#xD;
&#xD;
          -  Written informed consent and/or signed assent line from patient, parent or guardian&#xD;
&#xD;
          -  Negative pregnancy test in female patients of childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving prednisone &gt; 0.5 mg/kg/day at time of enrollment, or have received&#xD;
             anti-thymocyte globulin (ATG), donor lymphocyte infusion (DLI) or Campath within 28&#xD;
             days of enrollment&#xD;
&#xD;
          -  Patients with other uncontrolled infections; for bacterial infections, patients must&#xD;
             be receiving definitive therapy and have no signs of progressing infection for 72&#xD;
             hours prior to enrollment; for fungal infections patients must be receiving definitive&#xD;
             systemic anti-fungal therapy and have no signs of progressing infection for 1 week&#xD;
             prior to enrollment; progressing infection is defined as hemodynamic instability&#xD;
             attributable to sepsis or new symptoms, worsening physical signs or radiographic&#xD;
             findings attributable to infection; persisting fever without other signs or symptoms&#xD;
             will not be interpreted as progressing infection; patients with ongoing viral&#xD;
             infections are excluded&#xD;
&#xD;
          -  Patients with active acute GVHD grades II-IV&#xD;
&#xD;
          -  Active and uncontrolled relapse of malignancy&#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>Betul Oran</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Betul Oran</last_name>
      <phone>713-745-2820</phone>
      <email>boran@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Betul Oran</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT02210078
org study id: 2013-0657
secondary id: NCI-2014-01990
secondary id: 2013-0657
nct id: NCT02210078
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well donor cytomegalovirus-specific cytotoxic T-lymphocytes
      work in treating patients with a cytomegalovirus infection that has come back or has not
      gotten better despite standard therapy. White blood cells from donors who have been exposed
      to cytomegalovirus may be effective in treating patients with a cytomegalovirus infection.
PRIMARY OBJECTIVE:

      I. To assess the efficacy, feasibility and safety of administering most closely human
      leukocyte antigen (HLA)-matched cytomegalovirus (CMV) specific cytotoxic T-lymphocytes
      (HMC-CTLs) generated by "gamma-catch" to mediate antiviral activity in hematopoietic stem
      cell transplantation (HSCT) recipients with CMV infections.

      SECONDARY OBJECTIVE:

      I. To assess the persistency of the administered HMC-CTLs generated by "gamma-catch" and
      their contribution immune reconstitution.

      OUTLINE:

      Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes intravenously
      (IV). Patients with partial response, stable disease, or progressive disease may receive an
      additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum
      of 2 weeks from the first infusion.

      After completion of study treatment, patients are followed up periodically for 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Success, defined as R1 and R2 without treatment failure
time frame: Up to 4 weeks after second CTL infusion
description: The best outcome is defined as R1 = in complete response (CR) for 4 consecutive weeks, starting at week 2, without the need for a second cytotoxic T-lymphocyte (CTL) infusion. The second best outcome is defined as R2 = not in CR at week 2, 3, or 4, but in CR or partial response (PR) 4 weeks after the second CTL infusion.
measure: Overall survival time
time frame: Up to 12 months
description: Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.
measure: Disease-free survival time
time frame: Up to 12 months
description: Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.
measure: Graft-versus-host disease
time frame: Up to 12 months
description: Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression.
measure: Secondary graft failure
time frame: Up to 12 months
description: Will be analyzed as a function of patient covariates using standard statistical methods, including Bayesian survival regression analysis and ordinal regression.
arm group label: Treatment (allogeneic CMV-specific cytotoxic T-lymphocytes)
arm group type: Experimental
description: Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes IV. Patients with partial response, stable disease, or progressive disease may receive an additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum of 2 weeks from the first infusion.
intervention type: Biological
intervention name: Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes
description: Given IV
arm group label: Treatment (allogeneic CMV-specific cytotoxic T-lymphocytes)
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Betul Oran
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Cytomegalovirus Infections
mesh term: Neoplasms