<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/NCT04401410</url>
  </required_header>
  <id_info>
    <org_study_id>H-47739 BAT IT</org_study_id>
    <nct_id>NCT04401410</nct_id>
  </id_info>
  <brief_title>Anti-SARS Cov-2 T Cell Infusions for COVID 19</brief_title>
  <acronym>BATIT</acronym>
  <official_title>BAT IT: Banked Anti-SARS Cov-2 T Cell Infusions for Treatment of COVID 19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Center for Cell and Gene Therapy, Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>AlloVir</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Methodist Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Baylor College of Medicine</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a dose-finding safety trial followed by a randomized pilot trial comparing&#xD;
      administration of SARS-CoV2-specific T cells (SARS-CoVSTs) to standard of care treatment in&#xD;
      hospitalized patients with COVID19 who are at high risk of requiring mechanical ventilation.&#xD;
&#xD;
      The SARS-CoVSTs lines have been made at Baylor College of Medicine from healthy donors who&#xD;
      have made a full recovery from COVID19. These cell lines were frozen for later use and will&#xD;
      be thawed and used to treat patients who meet the eligibility criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The first part of this study is to identify the maximum tolerated dose (MTD) of allogeneic&#xD;
      SARS-CoV2-specific T cells (SARS-CoVSTs) for patients with COVID19 with high risk of&#xD;
      progression to mechanical ventilation.&#xD;
&#xD;
      The 3 dose levels (DL) are:&#xD;
&#xD;
      DL1: 1x10^7 cells (flat dose) DL2: 2x10^7 cells (flat dose) DL3: 4x10^7 cells (flat dose)&#xD;
&#xD;
      Enrollment to the dose escalation phase will be staggered. The first patient enrolled on each&#xD;
      of the 3 dose levels (DL1, DL2 and DL3) will have to complete the 14-day toxicity monitoring&#xD;
      window prior to enrollment of the next patients. Prior to dose escalation, all patients at a&#xD;
      particular dose level should have completed the minimum 14-day toxicity monitoring window&#xD;
      before enrolling to a higher dose level.&#xD;
&#xD;
      After the dose finding phase is complete and the MTD established, a randomized trial will be&#xD;
      conducted. Patient will be randomized 1:1 using the permuted block method with a block size&#xD;
      of 4 (2 in the treatment arm and 2 in the control arm) to receive treatment with SARS-CoVSTs&#xD;
      or routine treatment per institutional standards.&#xD;
&#xD;
      All enrolled patients will undergo the following evaluations:&#xD;
&#xD;
        -  Physical exam and history including height and weight&#xD;
&#xD;
        -  SARS-CoV-2 test&#xD;
&#xD;
        -  Blood tests&#xD;
&#xD;
        -  Chest X-ray or chest CT Scan if not already done in the past 48 hours.&#xD;
&#xD;
        -  A urine pregnancy test, when applicable&#xD;
&#xD;
      Patients randomized to receive SARS-CoVSTs will be pre-medicated with Benadryl and Tylenol.&#xD;
      The cells will be thawed and given through an intravenous line. Patients will be monitored&#xD;
      for infusion side effects for up to 14 days or until infusion side effects have completely&#xD;
      resolved, whichever is longer.&#xD;
&#xD;
      Blood will be drawn before the infusion and then up to daily for 14 days or until the patient&#xD;
      is discharged from the hospital. Optional blood samples will be drawn at 2, 3 and 6 months&#xD;
      after infusion. Study participation will last 6 months after the date of infusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to trial's eligibility criteria and the low census of hospitalized COVID-19 patients&#xD;
    meeting eligibility criteria, the Sponsor will be unable to enroll a meaningful number of&#xD;
    patients in this single-center trial in a reasonable time frame.&#xD;
  </why_stopped>
  <start_date type="Actual">November 4, 2020</start_date>
  <completion_date type="Actual">October 12, 2021</completion_date>
  <primary_completion_date type="Actual">October 12, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Escalation Phase: Rate of Dose Limiting Toxicities by CTCAE 5.0 [14 days post infusion]</measure>
    <time_frame>14 days post infusion</time_frame>
    <description>Defined as the proportion of subjects with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment. A dose limiting toxicity is defined as any acute GvHD (&gt; grade 2), grade ≥3 CRS or ICANS, grade ≥3 hematologic toxicity or grade ≥3 non-hematologic adverse events related to the T cell product within 14 days of the VST infusion and that are not due to pre-existing conditions as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Randomized Trial: Rate of Clinical Response as assessed by the World Health Organization (WHO) Ordinal Scale [7 days post-randomization or hospital discharge]</measure>
    <time_frame>7 Days post-randomization or at time of hospital discharge</time_frame>
    <description>Clinical Response rate is defined as the proportion of subjects reporting an increase in 2 or more points on the WHO Ordinal Scale. [Scored on a scale from 0 to 8; where 0 = Uninfected and 8 =Dead] or until patient is discharged.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Randomized Trial: Rate of Treatment-related adverse events (tAE) by CTCAE 5.0 [14 days post-randomization]</measure>
    <time_frame>14 days post-randomization</time_frame>
    <description>Defined as the proportion of subjects with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment. Treatment-related adverse events (tAE) are defined as any acute GvHD (&gt; grade 2), grade ≥3 CRS or ICANS, grade ≥3 hematologic toxicity or grade ≥3 non-hematologic adverse events related to the T cell product within 14 days of the VST infusion and that are not due to pre-existing conditions as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>SARS-CoV 2</condition>
  <condition>Viral Infection</condition>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>Dose Finding Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This phase is designed to evaluate the maximum tolerated dose (MTD) of partially HLA-matched SARS-CoVSTs administered to hospitalized COVID19 patients with high risk of progression to mechanical ventilation.&#xD;
The dose finding phase is a standard 3+3 safety study design. The 3 dose levels are:&#xD;
DL1: 1x10^7 cells (flat dose) DL2: 2x10^7 cells (flat dose) DL3: 4x10^7 cells (flat dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized Pilot - SARS-CoVSTs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized Pilot - Routine Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hospitalized patients with COVID-19 will be treated per current institutional guidelines.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Dose Finding Phase (MTD)</intervention_name>
    <description>Enrollment to the dose escalation phase will be staggered. The first patient enrolled on each of the 3 dose levels (DL1, DL2 and DL3) will have to complete the 14-day toxicity monitoring window prior to enrollment of the next patients. Prior to dose escalation, all patients at a particular dose level should have completed the minimum 14-day toxicity monitoring window before enrolling to a higher dose level.</description>
    <arm_group_label>Dose Finding Phase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Partially HLA-matched SARS-CoVSTs</intervention_name>
    <description>Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase</description>
    <arm_group_label>Randomized Pilot - SARS-CoVSTs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Routine care (no SARS-CoVSTs)</intervention_name>
    <description>Patients receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).</description>
    <arm_group_label>Randomized Pilot - Routine Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. SARS-CoV-2 infection confirmed by polymerase chain reaction assay (PCR) from a&#xD;
             nasopharyngeal swab or other accepted specimen type. (If testing was performed ≥ 5&#xD;
             days before enrollment, this must be repeated and accept only if positive again). Date&#xD;
             of COVID test must be ≤ 5 days prior to infusion.&#xD;
&#xD;
          2. Currently hospitalized adult patient (≥ 18 years of age) requiring medical care for&#xD;
             COVID19&#xD;
&#xD;
          3. Peripheral oxygen saturation (SpO2) ≥ 92% on room air&#xD;
&#xD;
          4. Hgb ≥ 7.0 gm/dl&#xD;
&#xD;
          5. Negative pregnancy test (if applicable)&#xD;
&#xD;
          6. Patient or parent/guardian capable of providing informed consent (may be obtained&#xD;
             electronically)&#xD;
&#xD;
          7. Evidence of pulmonary infiltrates on chest imaging. Any chest imaging findings which&#xD;
             would be consistent with COVID19 would qualify (Eg: ground glass opacities, multifocal&#xD;
             infiltrates etc.)&#xD;
&#xD;
          8. High risk of requiring mechanical ventilation as defined by at least two of the&#xD;
             following:&#xD;
&#xD;
               1. Age ≥ 60 years of age&#xD;
&#xD;
               2. Age ≥ 75 years of age (counts as meeting two criteria)&#xD;
&#xD;
               3. Hypertension (HTN)&#xD;
&#xD;
               4. Chronic cardiovascular disease other than HTN (eg: Coronary artery disease,&#xD;
                  congestive heart failure or cardiomyopathies).&#xD;
&#xD;
               5. Diabetes Mellitus&#xD;
&#xD;
               6. Obesity (BMI ≥ 30)&#xD;
&#xD;
               7. Obesity (BMI ≥ 40, counts as meeting two criteria)&#xD;
&#xD;
               8. Active cancer diagnosis or ongoing (within 3 months) cytotoxic chemo/&#xD;
                  radio-therapy for a cancer&#xD;
&#xD;
               9. Post-hematopoeitic stem cell or solid organ transplantation status&#xD;
&#xD;
              10. Immunodeficiency states including HIV infection on antiretroviral therapy (except&#xD;
                  those listed as exclusion criteria #1, #7 and #10) as determined by the treating&#xD;
                  physician (eg: receiving immunosuppressive therapy like rituximab or congenital&#xD;
                  immunodeficiency syndromes, prior treatment with chemotherapy greater than 3&#xD;
                  months ago but per investigators discretion could have lingering effects on the&#xD;
                  immune system, eg: chemotherapy regimens for lymphomas, ALL or AML etc.)&#xD;
&#xD;
              11. Chronic obstructive pulmonary disease (COPD)&#xD;
&#xD;
              12. Current everyday smoker&#xD;
&#xD;
              13. Chronic kidney disease (eGFR &lt; 30 mL/min/1.73 m2 )&#xD;
&#xD;
              14. Bronchial asthma (on active treatment prior to admission, eg. Use of rescue&#xD;
                  inhalers or inhaled corticosteroids or other treatments to prevent/treat&#xD;
                  attacks).&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Received Anti-thymocyte globulin (ATG), Campath or other T cell immunosuppressive&#xD;
             monoclonal antibodies in the 28 days prior to screening for enrollment&#xD;
&#xD;
          2. Requiring mechanical ventilation at time of T cell infusion&#xD;
&#xD;
          3. Alanine aminotransferase or aspartate aminotransferase greater than 5 x upper limit of&#xD;
             normal&#xD;
&#xD;
          4. If previously undergone an allogeneic hematopoietic stem cell transplant and have&#xD;
             evidence of active acute GVHD greater than or equal to grade 2&#xD;
&#xD;
          5. Uncontrolled relapse of malignancy&#xD;
&#xD;
          6. Requiring vasopressors&#xD;
&#xD;
          7. Known history of autoimmune disease except prior thyroiditis&#xD;
&#xD;
          8. Is not suitable at the discretion of the treating physician&#xD;
&#xD;
          9. Patients on greater than 6mg/day of dexamethasone (IV) or equivalent&#xD;
&#xD;
         10. Greater than grade 1 CRS per American Society for Transplantation and Cellular Therapy&#xD;
             (ASTCT) criteria&#xD;
&#xD;
         11. Patients should not be enrolled on any other interventional clinical trials for&#xD;
             COVID19. Patients may receive routine care for COVID19 per institutional standards&#xD;
             (including antivirals such as remdesivir or other FDA-EUA approved products and&#xD;
             thromboprophylaxis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Premal Lulla</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Houston Methodist Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>December 16, 2022</last_update_submitted>
  <last_update_submitted_qc>December 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
    <investigator_full_name>Premal Lulla</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>COVID 19</keyword>
  <keyword>SARS-CoV 2</keyword>
  <keyword>Viral infection</keyword>
  <keyword>Multivirus T cell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT04401410/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04401410
org study id: H-47739 BAT IT
nct id: NCT04401410
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a dose-finding safety trial followed by a randomized pilot trial comparing
      administration of SARS-CoV2-specific T cells (SARS-CoVSTs) to standard of care treatment in
      hospitalized patients with COVID19 who are at high risk of requiring mechanical ventilation.

      The SARS-CoVSTs lines have been made at Baylor College of Medicine from healthy donors who
      have made a full recovery from COVID19. These cell lines were frozen for later use and will
      be thawed and used to treat patients who meet the eligibility criteria.
The first part of this study is to identify the maximum tolerated dose (MTD) of allogeneic
      SARS-CoV2-specific T cells (SARS-CoVSTs) for patients with COVID19 with high risk of
      progression to mechanical ventilation.

      The 3 dose levels (DL) are:

      DL1: 1x10^7 cells (flat dose) DL2: 2x10^7 cells (flat dose) DL3: 4x10^7 cells (flat dose)

      Enrollment to the dose escalation phase will be staggered. The first patient enrolled on each
      of the 3 dose levels (DL1, DL2 and DL3) will have to complete the 14-day toxicity monitoring
      window prior to enrollment of the next patients. Prior to dose escalation, all patients at a
      particular dose level should have completed the minimum 14-day toxicity monitoring window
      before enrolling to a higher dose level.

      After the dose finding phase is complete and the MTD established, a randomized trial will be
      conducted. Patient will be randomized 1:1 using the permuted block method with a block size
      of 4 (2 in the treatment arm and 2 in the control arm) to receive treatment with SARS-CoVSTs
      or routine treatment per institutional standards.

      All enrolled patients will undergo the following evaluations:

        -  Physical exam and history including height and weight

        -  SARS-CoV-2 test

        -  Blood tests

        -  Chest X-ray or chest CT Scan if not already done in the past 48 hours.

        -  A urine pregnancy test, when applicable

      Patients randomized to receive SARS-CoVSTs will be pre-medicated with Benadryl and Tylenol.
      The cells will be thawed and given through an intravenous line. Patients will be monitored
      for infusion side effects for up to 14 days or until infusion side effects have completely
      resolved, whichever is longer.

      Blood will be drawn before the infusion and then up to daily for 14 days or until the patient
      is discharged from the hospital. Optional blood samples will be drawn at 2, 3 and 6 months
      after infusion. Study participation will last 6 months after the date of infusion.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Escalation Phase: Rate of Dose Limiting Toxicities by CTCAE 5.0 [14 days post infusion]
time frame: 14 days post infusion
description: Defined as the proportion of subjects with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment. A dose limiting toxicity is defined as any acute GvHD (> grade 2), grade ≥3 CRS or ICANS, grade ≥3 hematologic toxicity or grade ≥3 non-hematologic adverse events related to the T cell product within 14 days of the VST infusion and that are not due to pre-existing conditions as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.
measure: Randomized Trial: Rate of Clinical Response as assessed by the World Health Organization (WHO) Ordinal Scale [7 days post-randomization or hospital discharge]
time frame: 7 Days post-randomization or at time of hospital discharge
description: Clinical Response rate is defined as the proportion of subjects reporting an increase in 2 or more points on the WHO Ordinal Scale. [Scored on a scale from 0 to 8; where 0 = Uninfected and 8 =Dead] or until patient is discharged.
measure: Randomized Trial: Rate of Treatment-related adverse events (tAE) by CTCAE 5.0 [14 days post-randomization]
time frame: 14 days post-randomization
description: Defined as the proportion of subjects with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment. Treatment-related adverse events (tAE) are defined as any acute GvHD (> grade 2), grade ≥3 CRS or ICANS, grade ≥3 hematologic toxicity or grade ≥3 non-hematologic adverse events related to the T cell product within 14 days of the VST infusion and that are not due to pre-existing conditions as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.
arm group label: Dose Finding Phase
arm group type: Experimental
description: This phase is designed to evaluate the maximum tolerated dose (MTD) of partially HLA-matched SARS-CoVSTs administered to hospitalized COVID19 patients with high risk of progression to mechanical ventilation.
The dose finding phase is a standard 3+3 safety study design. The 3 dose levels are:
DL1: 1x10^7 cells (flat dose) DL2: 2x10^7 cells (flat dose) DL3: 4x10^7 cells (flat dose)
arm group label: Randomized Pilot - SARS-CoVSTs
arm group type: Experimental
description: Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection.
arm group label: Randomized Pilot - Routine Care
arm group type: Active Comparator
description: Hospitalized patients with COVID-19 will be treated per current institutional guidelines.
intervention type: Biological
intervention name: Dose Finding Phase (MTD)
description: Enrollment to the dose escalation phase will be staggered. The first patient enrolled on each of the 3 dose levels (DL1, DL2 and DL3) will have to complete the 14-day toxicity monitoring window prior to enrollment of the next patients. Prior to dose escalation, all patients at a particular dose level should have completed the minimum 14-day toxicity monitoring window before enrolling to a higher dose level.
arm group label: Dose Finding Phase
intervention type: Biological
intervention name: Partially HLA-matched SARS-CoVSTs
description: Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase
arm group label: Randomized Pilot - SARS-CoVSTs
intervention type: Other
intervention name: Routine care (no SARS-CoVSTs)
description: Patients receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).
arm group label: Randomized Pilot - Routine Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Premal Lulla
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Baylor College of Medicine
investigator full name: Premal Lulla
investigator title: Assistant Professor
mesh term: COVID-19
mesh term: Virus Diseases
provided document: 