<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/NCT03266653</url>
  </required_header>
  <id_info>
    <org_study_id>NYMC 581</org_study_id>
    <secondary_id>FD006363</secondary_id>
    <nct_id>NCT03266653</nct_id>
  </id_info>
  <brief_title>EBV-specific Cytotoxic T-lymphocytes (CTLs) for Refractory EBV Infection</brief_title>
  <official_title>A Pilot Study in the Treatment of Refractory Epstein-Barr Virus (EBV) Infection With Related Donor EBV Cytotoxic T-Lymphocytes 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>Indiana University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</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>
      Related donor Epstein-Barr Virus (EBV) specific cytotoxic T cells (CTLs) manufactured with&#xD;
      the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children,&#xD;
      adolescents and young adults with refractory EBV infection post Allogeneic Hematopoietic Stem&#xD;
      Cell 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">July 7, 2020</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 patients given identical treatment with CTLs for refractory EBV.</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 related to the infusion of EBV CTLs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Response to Treatment [Efficacy]</measure>
    <time_frame>Patients will be followed for 12 weeks after each infusion</time_frame>
    <description>Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Epstein-Barr Virus Infections</condition>
  <condition>Primary Immune Deficiency Disorder</condition>
  <arm_group>
    <arm_group_label>Refractory EBV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with refractory EBV will get one dose of EBV specific CTLs. If they don't show a response based on EBV PCRs, patients may get up to another 4 doses of EBV-CTLs (5 doses maximum)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cytotoxic t-lymphocytes</intervention_name>
    <description>EBV specific CTLs will be generated from HLA related matched and mismatched donors in a GMP facility and administered to the patient with refractory CTLs.</description>
    <arm_group_label>Refractory EBV</arm_group_label>
    <other_name>CTLs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Patients with Epstein-Barr virus infections post allogeneic HSCT, primary&#xD;
        immunodeficiencies or post solid organ transplant with:&#xD;
&#xD;
          -  Increasing or persistent quantitative EBV RT-PCR DNA copies despite two weeks of&#xD;
             appropriate anti-viral therapy and/or&#xD;
&#xD;
          -  progressive clinical symptoms attributable to EBV, including biopsy proven colitis,&#xD;
             lymphadenopathy, hepatomegaly, splenomegaly AND/OR&#xD;
&#xD;
          -  Medical intolerance to anti-viral therapies including:&#xD;
&#xD;
          -  intolerance to rituximab Consent: Written informed consent given (by patient or legal&#xD;
             representative) prior to any 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;
        2 Donor Eligibility 5.2.1 Related donor available with a T-cell response to the EBV MACS®&#xD;
        GMP PepTivator antigen(s) causing the therapy-refractory EBV infection.&#xD;
&#xD;
        a. Third Party Related Allogeneic Donor: If original donor is not available or does not&#xD;
        have a T-cell response: third party related allogeneic donor (family donor &gt; 1 HLA A, B, DR&#xD;
        match to recipient) with IgG positive to EBV and/or a T-cell response at least to the viral&#xD;
        MACS® GMP PepTivator EBV Select (containing among other antigens, NA-1, LMP2A and BZLF-1).&#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 CTL infusion&#xD;
        Patient receiving steroids (&gt;0.5 mg/kg prednisone equivalent) at the time of CTL infusion&#xD;
        Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion&#xD;
        Patient with poor performance status determined by Karnofsky (patients &gt;16 years) or Lansky&#xD;
        (patients ≤16 years) score ≤30% Concomitant enrollment in another experimental clinical&#xD;
        trial investigating the treatment of refractory EBV infection Any medical condition which&#xD;
        could compromise participation in the study according to the investigator's assessment&#xD;
        Known HIV infection Female patient of childbearing age who is pregnant or breast-feeding or&#xD;
        not willing to use an effective method of birth control 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 Cairo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York Medical College</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mitchell Cairo, MD</last_name>
    <phone>914-594-2150</phone>
    <email>mitchell_cairo@nymc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lauren Harrison</last_name>
    <phone>6172857844</phone>
    <email>lauren_harrison@nymc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's Hosptial 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>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>
  <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>Epstein-Barr Virus 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/NCT03266653
org study id: NYMC 581
secondary id: FD006363
nct id: NCT03266653
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Related donor Epstein-Barr Virus (EBV) specific cytotoxic T cells (CTLs) manufactured with
      the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children,
      adolescents and young adults with refractory EBV 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 patients given identical treatment with CTLs for refractory EBV.
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 related to the infusion of EBV CTLs
measure: Incidence of Response to Treatment [Efficacy]
time frame: Patients will be followed for 12 weeks after each infusion
description: Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs
arm group label: Refractory EBV
arm group type: Experimental
description: Patients with refractory EBV will get one dose of EBV specific CTLs. If they don't show a response based on EBV PCRs, patients may get up to another 4 doses of EBV-CTLs (5 doses maximum)
intervention type: Drug
intervention name: cytotoxic t-lymphocytes
description: EBV specific CTLs will be generated from HLA related matched and mismatched donors in a GMP facility and administered to the patient with refractory CTLs.
arm group label: Refractory EBV
other name: CTLs
criteria: 
gender: All
minimum age: 1 Month
maximum age: 30 Years
healthy volunteers: No
last name: Mitchell Cairo, MD
role: Principal Investigator
affiliation: New York Medical College
last name: Mitchell Cairo, MD
phone: 914-594-2150
email: mitchell_cairo@nymc.edu
last name: Lauren Harrison
phone: 6172857844
email: lauren_harrison@nymc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: 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: Communicable Diseases
mesh term: Epstein-Barr Virus Infections
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: Undecided