<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/NCT03266627</url>
  </required_header>
  <id_info>
    <org_study_id>NYMC 579</org_study_id>
    <secondary_id>FD006363</secondary_id>
    <nct_id>NCT03266627</nct_id>
  </id_info>
  <brief_title>Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection</brief_title>
  <official_title>A Pilot Study in the Treatment of Refractory Adenovirus (ADV) Infection With Related Donor ADV Cytotoxic T-Lymphocytes (ADV-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>University of Colorado, Denver</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>
  </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 Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the&#xD;
      Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in&#xD;
      children, adolescents and young adults with refractory ADV infection post Allogeneic&#xD;
      Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or&#xD;
      post solid organ 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 receive one dose of CTLs at the same dose. Patients who meet the criteria may need additional CTL doses up to 5 total.</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>12 weeks after each infusion</time_frame>
    <description>Patients will be followed for adverse events following each infusion of ADV CTLs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Response to Treatment (Efficacy)</measure>
    <time_frame>12 weeks after last infusion</time_frame>
    <description>Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Adenovirus</condition>
  <condition>Primary Immune Deficiency Disorder</condition>
  <arm_group>
    <arm_group_label>patients with adenoviral infection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cytotoxic t-lymphocytes</intervention_name>
    <description>adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.</description>
    <arm_group_label>patients with adenoviral infection</arm_group_label>
    <other_name>viral specific CTLs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Patients with Adenovirus infections post allogeneic HSCT, with primary&#xD;
             immunodeficiencies or post solid organ transplant with:&#xD;
&#xD;
               -  Increasing or persistent quantitative ADV RT-PCR DNA copies despite two weeks of&#xD;
                  appropriate anti-viral therapy and/or&#xD;
&#xD;
               -  clinical symptoms attributed to adenovirus, including pneumonitis, hemorrhagic&#xD;
                  cystitis, colitis, hepatitis AND/OR&#xD;
&#xD;
               -  Medical intolerance to anti-viral therapies including:&#xD;
&#xD;
                    -  grade 2 renal insufficiency secondary to cidofovir Consent: Written informed&#xD;
                       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 30.00&#xD;
             years&#xD;
&#xD;
             Females of childbearing potential with a negative urine pregnancy test&#xD;
&#xD;
          2. Donor Eligibility Related donor available with a T-cell response to the viral MACS®&#xD;
             GMP PepTivator antigen(s) of adenovirus.&#xD;
&#xD;
             a. Third Party Related Allogeneic Donor: If original donor is not available or does&#xD;
             not have a T-cell response: third party allogeneic donor (family donor &gt; 1 HLA A, B,&#xD;
             DR match to recipient) with a T-cell response at least to the viral MACS® GMP&#xD;
             PepTivator antigen(s) of adenovirus.&#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&#xD;
             prior to 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 adenovirus infection(s) Any medical&#xD;
        condition which could compromise participation in the study according to the investigator's&#xD;
        assessment Known HIV infection Female patient of childbearing age who is pregnant or&#xD;
        breast-feeding or not willing to use an effective method of birth control during study&#xD;
        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;
&#xD;
        -&#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, RN</last_name>
    <phone>617-285-7844</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>Children's Hospital of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Verneris, MD</last_name>
      <phone>720-777-1234</phone>
      <email>Michael.Verneris@childrenscolorado.org</email>
    </contact>
    <contact_backup>
      <last_name>Amanda Kinderman, MPH</last_name>
      <phone>303-724-3652</phone>
      <email>amanda.kinderman@ucdenver.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Verneris, MD</last_name>
      <email>MICHAEL.VERNERIS@CUANSCHUTZ.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>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 29, 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>adenovirus</keyword>
  <keyword>primary immune deficiency disorder</keyword>
  <keyword>cytotoxic t-lymphocytes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoviridae 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/NCT03266627
org study id: NYMC 579
secondary id: FD006363
nct id: NCT03266627
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the
      Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in
      children, adolescents and young adults with refractory ADV 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 receive one dose of CTLs at the same dose. Patients who meet the criteria may need additional CTL doses up to 5 total.
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: 12 weeks after each infusion
description: Patients will be followed for adverse events following each infusion of ADV CTLs
measure: Incidence of Response to Treatment (Efficacy)
time frame: 12 weeks after last infusion
description: Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs
arm group label: patients with adenoviral infection
arm group type: Experimental
description: patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.
intervention type: Drug
intervention name: cytotoxic t-lymphocytes
description: adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.
arm group label: patients with adenoviral infection
other name: viral specific 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, RN
phone: 617-285-7844
email: lauren_harrison@nymc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
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: Adenoviridae Infections
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: Undecided