<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/NCT03266640</url>
  </required_header>
  <id_info>
    <org_study_id>NYMC 580</org_study_id>
    <secondary_id>FD006363</secondary_id>
    <nct_id>NCT03266640</nct_id>
  </id_info>
  <brief_title>Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)</brief_title>
  <official_title>A Pilot Study in the Treatment of Refractory Cytomegalovirus (CMV) Infections With Related Donor CMV Specific Cytotoxic T-cells (CTLs) in Children, Adolescents and Young Adult Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York Medical College</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York Medical College</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine&#xD;
      Capture System will be administered in children, adolescents and young adults (CAYA) with&#xD;
      refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell&#xD;
      Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ&#xD;
      transplant.&#xD;
&#xD;
      Funding Source: FDA OOPD&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">December 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>
    <intervention_model_description>All eligible patients will be given CMV specific CTLs and dose is based on donor source: HLA matched and HLA mismatced</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
    <time_frame>Patients will be followed for 12 weeks after each infusion</time_frame>
    <description>Patients will be monitored for adverse events following the administration of CMV CTLs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Response to Treatment</measure>
    <time_frame>Patients will be followed 12 weeks after each infusion</time_frame>
    <description>Patients will be followed for improvement in viral infection by monitoring CMV PCR weekly for response to treatment with CTLs</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Cytomegalovirus Infections</condition>
  <condition>Primary Immune Deficiency Disorder</condition>
  <arm_group>
    <arm_group_label>Refractory CMV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>viral specific cytotoxic t-lymphocytes</intervention_name>
    <description>CMV specific CTLs will be collected from HLA matched or mismatched donors and manufactured in a GMP facility and administered to patients with refractory CMV infection.</description>
    <arm_group_label>Refractory CMV</arm_group_label>
    <other_name>CMV CTLs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Patients with refractory CMV infection post allogeneic HSCT, with primary&#xD;
        immunodeficiencies or post solid organ transplant with either&#xD;
&#xD;
          -  Increasing or persistent quantitative qRT-PCR DNA copies despite two weeks of&#xD;
             appropriate anti-viral therapy AND/OR&#xD;
&#xD;
          -  Medical intolerance to anti-viral therapies including:&#xD;
&#xD;
          -  ANC &lt; 500/mm2 secondary to ganciclovir&#xD;
&#xD;
               -  2 renal toxicity with foscarnet And/or&#xD;
&#xD;
          -  known resistance to ganciclovir and/or foscarnet&#xD;
&#xD;
        Consent: Written informed consent given (by patient or legal representative) prior to any&#xD;
        study-related procedures.&#xD;
&#xD;
        Performance Status &gt; 30% (Lansky &lt; 16 yrs and Karnofsky &gt; 16 yrs) Age: 0.1 to 30.99 years&#xD;
        Females of childbearing potential with a negative urine pregnancy test&#xD;
&#xD;
        Donor Eligibility Related donor available with a T-cell response to the CMV MACS® GMP&#xD;
        PepTivator antigen(s).&#xD;
&#xD;
        a. Third Party Allogeneic Donor: If original donor is not available or does not have a&#xD;
        T-cell response: third party related allogeneic donor (family donor &gt; 1 HLA A, B, DR match&#xD;
        to recipient) with IgG positive to CMV and/or a T-cell response to the CMV MACS® GMP&#xD;
        PepTivator .&#xD;
&#xD;
        AND Allogeneic donor disease screening is complete similar to hematopoietic stem cell&#xD;
        donors (Appendix 1).&#xD;
&#xD;
        AND Obtained informed consents by donor or donor legally authorized representative prior to&#xD;
        donor collection.&#xD;
&#xD;
        3 Patient exclusion criteria:&#xD;
&#xD;
        A patient meeting any of the following criteria is not eligible for the present study:&#xD;
&#xD;
        Patient with acute GVHD &gt; grade 2 or extensive chronic GVHD at the time of CMV CTL infusion&#xD;
        Patient receiving steroids (&gt;0.5 mg/kg prednisone equivalent) at the time of CMV CTL&#xD;
        infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CMV&#xD;
        CTL infusion Thymoglobulin (ATG), Alemtuzumab or T cell immunosuppressive monoclonal&#xD;
        antibodies within 30 days Patient with poor performance status determined by Karnofsky&#xD;
        (patients &gt;16 years) or Lansky (patients ≤16 years) score ≤30% CMV retinitis Concomitant&#xD;
        enrollment in another experimental clinical trial investigating the treatment of refractory&#xD;
        CMV infection.&#xD;
&#xD;
        Any medical condition which could compromise participation in the study according to the&#xD;
        investigator's assessment Known HIV infection Female patient of childbearing age who is&#xD;
        pregnant or breast-feeding or not willing to use an effective method of birth control&#xD;
        during study treatment.&#xD;
&#xD;
        Known hypersensitivity to iron dextran Patients unwilling or unable to comply with the&#xD;
        protocol or unable to give informed consent.&#xD;
&#xD;
        Known human anti-mouse antibodies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mitchell S Cairo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York Medical College</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mitchell S Cairo, MD</last_name>
    <phone>914-594-2150</phone>
    <email>mitchell_cairo@nymc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lauren Harrison, RN</last_name>
    <phone>6172857844</phone>
    <email>lauren_harrison@nymc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neena Kapoor, MD</last_name>
      <email>nkapoor@chla.usc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julia Chu, MD</last_name>
      <email>Julia.Chu2@ucsf.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kenneth Cooke, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shalini Shenoy, MD</last_name>
      <email>shalinishenoy@wustl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mitchell S Cairo, MD</last_name>
      <phone>914-594-2150</phone>
      <email>mitchell_cairo@nymc.edu</email>
    </contact>
    <investigator>
      <last_name>Mitchell S. Cairo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hosptial</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dean Lee, MD, PhD</last_name>
      <phone>614-722-3550</phone>
      <email>Dean.Lee@nationwidechildrens.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nancy Bunin, MD</last_name>
      <phone>215-590-2255</phone>
      <email>buninn@email.chop.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin/Children's Hospital of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie A Talano, MD</last_name>
      <phone>414-955-4185</phone>
      <email>jtalano@mcw.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kathy Jodarski</last_name>
      <phone>414-266-2681</phone>
      <email>kjodarski@chw.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>June 25, 2023</last_update_submitted>
  <last_update_submitted_qc>June 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York Medical College</investigator_affiliation>
    <investigator_full_name>Mitchell Cairo</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Cytomegalovirus</keyword>
  <keyword>CMV</keyword>
  <keyword>cytotoxic t-lymphocytes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Cytomegalovirus Infections</mesh_term>
    <mesh_term>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</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/NCT03266640
org study id: NYMC 580
secondary id: FD006363
nct id: NCT03266640
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine
      Capture System will be administered in children, adolescents and young adults (CAYA) with
      refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell
      Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ
      transplant.

      Funding Source: FDA OOPD
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All eligible patients will be given CMV specific CTLs and dose is based on donor source: HLA matched and HLA mismatced
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: Patients will be followed for 12 weeks after each infusion
description: Patients will be monitored for adverse events following the administration of CMV CTLs
measure: Incidence of Response to Treatment
time frame: Patients will be followed 12 weeks after each infusion
description: Patients will be followed for improvement in viral infection by monitoring CMV PCR weekly for response to treatment with CTLs
arm group label: Refractory CMV
arm group type: Experimental
description: Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.
intervention type: Drug
intervention name: viral specific cytotoxic t-lymphocytes
description: CMV specific CTLs will be collected from HLA matched or mismatched donors and manufactured in a GMP facility and administered to patients with refractory CMV infection.
arm group label: Refractory CMV
other name: CMV CTLs
criteria: 
gender: All
minimum age: 1 Month
maximum age: 30 Years
healthy volunteers: No
last name: Mitchell S Cairo, MD
role: Principal Investigator
affiliation: New York Medical College
last name: Mitchell S Cairo, MD
phone: 914-594-2150
email: mitchell_cairo@nymc.edu
last name: Lauren Harrison, RN
phone: 6172857844
email: lauren_harrison@nymc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York Medical College
investigator full name: Mitchell Cairo
investigator title: Principal Investigator
mesh term: Infections
mesh term: Cytomegalovirus Infections
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: Undecided