xml: <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/NCT06027879</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY23030062</org_study_id>
      <nct_id>NCT06027879</nct_id>
    </id_info>
    <brief_title>Anti-viral T-cell Therapy by Gamma Capture</brief_title>
    <acronym>Gamma Capture</acronym>
    <official_title>Anti-viral T-cell Therapy by Gamma Capture for High-risk Patients With Acquired or Inherited Immune Defects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Paul Szabolcs</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Pittsburgh</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>
        The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥1/6&#xD;
        Human Leukocyte Antigens (HLA) -matched, viral specific T cells have efficacy against&#xD;
        adenovirus, Cytomegalovirus (CMV), and Epstein Barr Virus (EBV) in subjects who have&#xD;
        previously received any type of allogeneic Hematopoietic Cell transplant (HCT) or solid organ&#xD;
        transplant (SOT) or have compromised immunity. Reconstitution of anti-viral immunity by&#xD;
        donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections&#xD;
        with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products,&#xD;
        and cost associated with products that may not be used limits their value. This trial will&#xD;
        evaluate viral specific T cells generated by gamma capture technology. Eligible patients will&#xD;
        include HCT and/or SOT recipients, and/or patients with compromised immunity who have&#xD;
        adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard&#xD;
        therapy. Infusion of the cellular product will be assessed for safety and efficacy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Ideally, subjects will receive up to ≤1 x 105 (100,000) viable CD3 cells/kg however actual&#xD;
        cell dose of infusion will be based upon available cells and subject's clinical picture.&#xD;
        Historically, subjects have received all available cells after the gamma capture procedure.&#xD;
  &#xD;
        Two-weeks post initial cellular infusion, subject may be eligible to receive additional&#xD;
        cellular infusions. If so, either the same or an alternative donor may be considered however,&#xD;
        a subject will not receive more than 3 infusions from one donor or exceed 6 infusions in&#xD;
        total from all donors. Infusions will be a minimum of 14-days apart. Subjects will not&#xD;
        receive additional infusions if they exhibit Graft Versus Host Disease (GvHD) or Cytokine&#xD;
        Release Syndrome (CRS) Grade II or higher, according to CTCAE v5.&#xD;
  &#xD;
        If a subject is to receive a second infusion, eligibility and baseline data collection will&#xD;
        not be repeated for the recipient or original donor, unless necessary per institutional&#xD;
        guidelines. Should an alternative donor be selected for an infusion, eligibility of the new&#xD;
        donor will need confirmed. Pregnant donors may be considered if medically suitable.&#xD;
  &#xD;
        Two weeks post-initial cellular infusion, the following criteria will be assessed to&#xD;
        determine if additional infusions are necessary:&#xD;
  &#xD;
          -  Complete response: Return to normal range as defined by specific assay used and clinical&#xD;
             signs and symptoms. These subjects are not eligible to receive an additional cellular&#xD;
             infusion.&#xD;
  &#xD;
          -  Partial response: Decrease in viral load of at least 50% from baseline or significant&#xD;
             improvement of clinical signs. The clinical response is further defined as meeting one&#xD;
             or more of the following criteria and no worsening in any of the others:&#xD;
  &#xD;
               1. Absence of fever, if fever is present at baseline&#xD;
  &#xD;
               2. No need for pressors, if on pressors at baseline&#xD;
  &#xD;
               3. No need for oxygen and/or mechanical ventilation, if needed at baseline&#xD;
  &#xD;
               4. Decrease in stool output, if is diarrhea present at baseline&#xD;
  &#xD;
        These subjects may receive additional cellular infusions as clinically indicated:&#xD;
  &#xD;
          -  Stable disease: Changes insufficient to qualify as partial response or progression.&#xD;
             These subjects are eligible to receive additional cellular infusions.&#xD;
  &#xD;
          -  Progression: Increase in viral load of at least 50% from baseline or dissemination to&#xD;
             other sites of disease. These subjects are eligible to receive additional cellular&#xD;
             infusions.&#xD;
  &#xD;
        Subjects are followed for six months post initial viral-specific T cell infusion. If a&#xD;
        subject receives additional infusions, GVHD and adverse events only will be followed for a&#xD;
        minimum of three months from last infusion, even if extending beyond the six-month follow-up&#xD;
        from the first infusion. Data may be abstracted from subjects' medical charts for an&#xD;
        additional 1 year after most recent viral-specific T cell infusion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2028</primary_completion_date>
    <phase>Phase 1/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>Grade III-IV Acute GvHD</measure>
      <time_frame>Day 0</time_frame>
      <description>The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Grade III-IV Acute GvHD</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Grade III-IV Acute GvHD</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Grade III-IV Acute GvHD</measure>
      <time_frame>6 month from first cellular infusion</time_frame>
      <description>The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>Rate of Elimination or reduction of oxygen dependence identified at baseline</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>Rate of Resolution of fever, attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of radiographic findings attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>1 month from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>Rate of Elimination or reduction of oxygen dependence identified at baseline</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>Rate of Resolution of fever, attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of radiographic findings attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>3 month from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>Rate of Elimination or reduction of oxygen dependence identified at baseline</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>Rate of Resolution of fever, attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of radiographic findings attributable to viral disease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical response to treatment of viral infection</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>1-year overall survival from first cellular infusion (continuous)</measure>
      <time_frame>First cellular infusion to 1 year post first cellular infusion</time_frame>
      <description>Number of deaths that occurred from treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Graft rejection</measure>
      <time_frame>3 months after last cellular infusion</time_frame>
      <description>How frequent, if any, graft rejection occurs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Graft rejection</measure>
      <time_frame>6 months after last cellular infusion</time_frame>
      <description>How frequent, if any, graft rejection occurs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Mechanical ventilation exceeding 48 hours</measure>
      <time_frame>3 months after last cellular infusion</time_frame>
      <description>How long, if any</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Mechanical ventilation exceeding 48 hours</measure>
      <time_frame>6 months after last cellular infusion</time_frame>
      <description>How long, if any</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Usage of concomitant antiviral agents</measure>
      <time_frame>First cellular infusion to 1 year post first cellular infusion</time_frame>
      <description>The introduction of concomitant antiviral medication post infusion, if any</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immune reconstitution with focus on adaptive T cell immunity and viral-specific responses</measure>
      <time_frame>1 month following first cellular infusion</time_frame>
      <description>The pace of systemic immune reconstitution, measured by the increased number of CD4+ T lymphocytes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immune reconstitution with focus on adaptive T cell immunity and viral-specific responses</measure>
      <time_frame>3 months following first cellular infusion</time_frame>
      <description>The pace of systemic immune reconstitution, measured by the increased number of CD4+ T lymphocytes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of severe or extensive chronic GVHD</measure>
      <time_frame>6 months from first cellular infusion</time_frame>
      <description>The number of patients who develop chronic graft versus host disease (GVHD) post first infusion based on Clinical Chronic GvHD Assessment</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Adenovirus</condition>
    <condition>Cytomegalovirus Infections</condition>
    <condition>Epstein-Barr Virus Infections</condition>
    <arm_group>
      <arm_group_label>Viral Specific T-Lymphocytes</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Viral Specific T-Lymphocytes Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Specific T- Lymphocytes</intervention_name>
      <description>Peripheral blood mononuclear cells will be collected from the donor and loaded onto Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.</description>
      <arm_group_label>Viral Specific T-Lymphocytes</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient, parent, or legal guardian must have given written informed consent, according&#xD;
               to FDA guidelines. For pediatric subject who are developmentally able, assent or&#xD;
               affirmation will be obtained, if feasible.&#xD;
  &#xD;
            2. Male or female, 1 month through 65 years old, inclusive, at the time of informed&#xD;
               consent.&#xD;
  &#xD;
            3. Prior allogeneic hematopoietic stem cell transplant (bone marrow, peripheral blood&#xD;
               stem cells, single or double cord blood), OR prior solid organ transplant (liver,&#xD;
               kidney, lung and/or heart, intestinal, or multivisceral), OR diagnosis of primary&#xD;
               immunodeficiency OR current/recent administration of immunosuppressive therapy for&#xD;
               cancer or autoimmune disease.&#xD;
  &#xD;
            4. Negative pregnancy test for females ≥10 years old or who have reached menarche, unless&#xD;
               surgically sterilized. All females of childbearing potential and lactation must agree&#xD;
               to use an FDA approved method of birth control for the duration of their&#xD;
               participation.&#xD;
  &#xD;
            5. Clinical status, at the time of consent, amendable to tapering of steroids to less&#xD;
               than 1 mg/kg/day prednisone (or equivalent) prior to cellular infusion.&#xD;
  &#xD;
            6. Diagnosis of Adenovirus, CMV, or EBV infection, persistent despite standard therapy.&#xD;
  &#xD;
          A. Adenovirus Infection or Disease:&#xD;
  &#xD;
            1. Active adenovirus infection: (i.e. gastroenteritis, pneumonia, hemorrhagic cystitis,&#xD;
               hepatitis, pancreatitis, meningitis) defined as the demonstration of adenovirus by&#xD;
               biopsy specimen from affected site(s) (by culture or histology), or the detection of&#xD;
               adenovirus by culture, PCR or direct fluorescent antibody stain in fluid in the&#xD;
               presence of worsening or persistent clinical or imaging findings despite at least 14&#xD;
               days of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other&#xD;
               available pharmacological agents) OR&#xD;
  &#xD;
            2. Refractory adenoviremia: defined as DNAemia &gt;5000 copies/mL or &lt;1 log decrease after&#xD;
               at least 2 weeks of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or&#xD;
               other available pharmacological agents) OR&#xD;
  &#xD;
            3. Intolerance of or contraindication to antiviral medications.&#xD;
  &#xD;
          B.CMV Infection or Disease:&#xD;
  &#xD;
            1. Active CMV infection: (i.e. pneumonia, meningitis, retinitis, hepatitis, hemorrhagic&#xD;
               cystitis, and/or gastroenteritis) defined as the demonstration of CMV by biopsy&#xD;
               specimen from affected site(s) (by culture or histology) or the detection of CMV by&#xD;
               culture, PCR or direct fluorescent antibody stain in fluid in the presence of&#xD;
               worsening or persistent clinical or imaging findings despite at least 14 days of&#xD;
               appropriate antiviral therapy (i.e. Foscarnet, ganciclovir, cidofovir, or other&#xD;
               available pharmacological agents) OR&#xD;
  &#xD;
            2. Refractory CMV viremia: defined as the continued presence of DNAemia, with ≥2,000&#xD;
               IU/mL or &lt;1 log decrease after at least 14 days of appropriate antiviral therapy (i.e.&#xD;
               Foscarnet, ganciclovir, cidofovir, or other available pharmacological agents) OR&#xD;
  &#xD;
            3. Intolerance of or contraindication to antiviral medications.&#xD;
  &#xD;
          C. EBV Infection or Disease:&#xD;
  &#xD;
            1. Biopsy proven lymphoma or posttransplant lymphoproliferative disease with EBV genomes&#xD;
               detected in tumor cells by immunocytochemistry (i.e. EBER positive) or in situ PCR, OR&#xD;
  &#xD;
            2. Clinical or imaging findings consistent with EBV lymphoma and associated elevated EBV&#xD;
               viral load in peripheral blood in a patient where biopsy is deemed too high risk, OR&#xD;
  &#xD;
            3. Failure of antiviral therapy, as determined by one of the two bullets below after&#xD;
               three weeks of anti-CD20 targeted therapy such as Rituximab.&#xD;
  &#xD;
          i. There was an increase or less than 50% response at sites of lymphoma disease or&#xD;
          lymphoproliferation.&#xD;
  &#xD;
          ii. There was a rise or a fall of less than 50% in EBV viral load in peripheral blood of&#xD;
          PTLD patients.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Received Antithymocyte Globulin (ATG) or Alemtuzumab within 28 days of viral-specific&#xD;
               T cell infusion and a lack of evidence of T cell survival, defined by &lt;10 CD3+ T&#xD;
               cells/uL (in unique situations, plasmapheresis may be considered).&#xD;
  &#xD;
            2. Active acute GVHD grades II-IV.&#xD;
  &#xD;
            3. Received donor lymphocyte infusion, with the exception of a fraction of an umbilical&#xD;
               cord blood, within 14 days of viral-specific T cell infusion. Subjects receiving a&#xD;
               fraction of an umbilical cord blood within 14 days of the viral-specific T cell&#xD;
               infusion will not be excluded.&#xD;
  &#xD;
            4. Active and uncontrolled relapse of malignancy (other than EBV+ post-transplant&#xD;
               lymphoproliferative disorder or lymphoma).&#xD;
  &#xD;
            5. Received an investigational product in the preceding 2 weeks (prior to infusion) that&#xD;
               may impact Viral Specific T-cells (VST) survival.&#xD;
  &#xD;
            6. Females of child bearing potential must not be lactating.&#xD;
  &#xD;
            7. Past or current medical problems or findings from physical examination or laboratory&#xD;
               testing that are not listed above, which, in the opinion of the investigator, may pose&#xD;
               additional risks to participation in the study, may interfere with the participant's&#xD;
               ability to comply with study requirements, or that may impact the quality or&#xD;
               interpretation of the data obtained from the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Month</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Paul Szabolcs, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Pittsburgh</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Paul Szabolcs, MD</last_name>
      <phone>412-692-6225</phone>
      <email>paul.szabolcs@chp.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Shawna McIntyre, RN</last_name>
      <phone>412-692-5552</phone>
      <email>Mcintyresm@upmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>UPMC Children's Hospital of Pittsburgh</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15224</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>Paul Szabolcs</investigator_full_name>
      <investigator_title>Chief, Division of Blood and Marrow Transplantation and Cellular Therapies, Medical Director of the Stem Cell Laboratory</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>Cytomegalovirus Infections</mesh_term>
      <mesh_term>Epstein-Barr Virus Infections</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06027879
  org study id: STUDY23030062
  nct id: NCT06027879
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥1/6
        Human Leukocyte Antigens (HLA) -matched, viral specific T cells have efficacy against
        adenovirus, Cytomegalovirus (CMV), and Epstein Barr Virus (EBV) in subjects who have
        previously received any type of allogeneic Hematopoietic Cell transplant (HCT) or solid organ
        transplant (SOT) or have compromised immunity. Reconstitution of anti-viral immunity by
        donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections
        with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products,
        and cost associated with products that may not be used limits their value. This trial will
        evaluate viral specific T cells generated by gamma capture technology. Eligible patients will
        include HCT and/or SOT recipients, and/or patients with compromised immunity who have
        adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard
        therapy. Infusion of the cellular product will be assessed for safety and efficacy.
  Ideally, subjects will receive up to ≤1 x 105 (100,000) viable CD3 cells/kg however actual
        cell dose of infusion will be based upon available cells and subject's clinical picture.
        Historically, subjects have received all available cells after the gamma capture procedure.
  
        Two-weeks post initial cellular infusion, subject may be eligible to receive additional
        cellular infusions. If so, either the same or an alternative donor may be considered however,
        a subject will not receive more than 3 infusions from one donor or exceed 6 infusions in
        total from all donors. Infusions will be a minimum of 14-days apart. Subjects will not
        receive additional infusions if they exhibit Graft Versus Host Disease (GvHD) or Cytokine
        Release Syndrome (CRS) Grade II or higher, according to CTCAE v5.
  
        If a subject is to receive a second infusion, eligibility and baseline data collection will
        not be repeated for the recipient or original donor, unless necessary per institutional
        guidelines. Should an alternative donor be selected for an infusion, eligibility of the new
        donor will need confirmed. Pregnant donors may be considered if medically suitable.
  
        Two weeks post-initial cellular infusion, the following criteria will be assessed to
        determine if additional infusions are necessary:
  
          -  Complete response: Return to normal range as defined by specific assay used and clinical
             signs and symptoms. These subjects are not eligible to receive an additional cellular
             infusion.
  
          -  Partial response: Decrease in viral load of at least 50% from baseline or significant
             improvement of clinical signs. The clinical response is further defined as meeting one
             or more of the following criteria and no worsening in any of the others:
  
               1. Absence of fever, if fever is present at baseline
  
               2. No need for pressors, if on pressors at baseline
  
               3. No need for oxygen and/or mechanical ventilation, if needed at baseline
  
               4. Decrease in stool output, if is diarrhea present at baseline
  
        These subjects may receive additional cellular infusions as clinically indicated:
  
          -  Stable disease: Changes insufficient to qualify as partial response or progression.
             These subjects are eligible to receive additional cellular infusions.
  
          -  Progression: Increase in viral load of at least 50% from baseline or dissemination to
             other sites of disease. These subjects are eligible to receive additional cellular
             infusions.
  
        Subjects are followed for six months post initial viral-specific T cell infusion. If a
        subject receives additional infusions, GVHD and adverse events only will be followed for a
        minimum of three months from last infusion, even if extending beyond the six-month follow-up
        from the first infusion. Data may be abstracted from subjects' medical charts for an
        additional 1 year after most recent viral-specific T cell infusion.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Grade III-IV Acute GvHD
  time frame: Day 0
  description: The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
  measure: Grade III-IV Acute GvHD
  time frame: 1 month from first cellular infusion
  description: The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
  measure: Grade III-IV Acute GvHD
  time frame: 3 month from first cellular infusion
  description: The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
  measure: Grade III-IV Acute GvHD
  time frame: 6 month from first cellular infusion
  description: The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
  measure: Clinical response to treatment of viral infection
  time frame: 1 month from first cellular infusion
  description: Rate of Elimination or reduction of oxygen dependence identified at baseline
  measure: Clinical response to treatment of viral infection
  time frame: 1 month from first cellular infusion
  description: Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily
  measure: Clinical response to treatment of viral infection
  time frame: 1 month from first cellular infusion
  description: Rate of Resolution of fever, attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 1 month from first cellular infusion
  description: Rate of Resolution or improvement of radiographic findings attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 1 month from first cellular infusion
  description: Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis
  measure: Clinical response to treatment of viral infection
  time frame: 3 month from first cellular infusion
  description: Rate of Elimination or reduction of oxygen dependence identified at baseline
  measure: Clinical response to treatment of viral infection
  time frame: 3 month from first cellular infusion
  description: Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily
  measure: Clinical response to treatment of viral infection
  time frame: 3 month from first cellular infusion
  description: Rate of Resolution of fever, attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 3 month from first cellular infusion
  description: Rate of Resolution or improvement of radiographic findings attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 3 month from first cellular infusion
  description: Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis
  measure: Clinical response to treatment of viral infection
  time frame: 6 months from first cellular infusion
  description: Rate of Elimination or reduction of oxygen dependence identified at baseline
  measure: Clinical response to treatment of viral infection
  time frame: 6 months from first cellular infusion
  description: Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily
  measure: Clinical response to treatment of viral infection
  time frame: 6 months from first cellular infusion
  description: Rate of Resolution of fever, attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 6 months from first cellular infusion
  description: Rate of Resolution or improvement of radiographic findings attributable to viral disease
  measure: Clinical response to treatment of viral infection
  time frame: 6 months from first cellular infusion
  description: Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis
  measure: 1-year overall survival from first cellular infusion (continuous)
  time frame: First cellular infusion to 1 year post first cellular infusion
  description: Number of deaths that occurred from treatment
  measure: Incidence of Graft rejection
  time frame: 3 months after last cellular infusion
  description: How frequent, if any, graft rejection occurs
  measure: Incidence of Graft rejection
  time frame: 6 months after last cellular infusion
  description: How frequent, if any, graft rejection occurs
  measure: Incidence of Mechanical ventilation exceeding 48 hours
  time frame: 3 months after last cellular infusion
  description: How long, if any
  measure: Incidence of Mechanical ventilation exceeding 48 hours
  time frame: 6 months after last cellular infusion
  description: How long, if any
  measure: Usage of concomitant antiviral agents
  time frame: First cellular infusion to 1 year post first cellular infusion
  description: The introduction of concomitant antiviral medication post infusion, if any
  measure: Immune reconstitution with focus on adaptive T cell immunity and viral-specific responses
  time frame: 1 month following first cellular infusion
  description: The pace of systemic immune reconstitution, measured by the increased number of CD4+ T lymphocytes.
  measure: Immune reconstitution with focus on adaptive T cell immunity and viral-specific responses
  time frame: 3 months following first cellular infusion
  description: The pace of systemic immune reconstitution, measured by the increased number of CD4+ T lymphocytes.
  measure: Incidence of severe or extensive chronic GVHD
  time frame: 6 months from first cellular infusion
  description: The number of patients who develop chronic graft versus host disease (GVHD) post first infusion based on Clinical Chronic GvHD Assessment
  arm group label: Viral Specific T-Lymphocytes
  arm group type: Experimental
  description: Viral Specific T-Lymphocytes Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.
  intervention type: Biological
  intervention name: Specific T- Lymphocytes
  description: Peripheral blood mononuclear cells will be collected from the donor and loaded onto Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.
  arm group label: Viral Specific T-Lymphocytes
  criteria: 
  gender: All
  minimum age: 1 Month
  maximum age: 65 Years
  healthy volunteers: No
  last name: Paul Szabolcs, MD
  role: Principal Investigator
  affiliation: University of Pittsburgh
  last name: Paul Szabolcs, MD
  phone: 412-692-6225
  email: paul.szabolcs@chp.edu
  last name: Shawna McIntyre, RN
  phone: 412-692-5552
  email: Mcintyresm@upmc.edu
  facility: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: Paul Szabolcs
  investigator title: Chief, Division of Blood and Marrow Transplantation and Cellular Therapies, Medical Director of the Stem Cell Laboratory
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Cytomegalovirus Infections
  mesh term: Epstein-Barr Virus Infections
  sharing ipd: No