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Anti-SARS Cov-2 T Cell Infusions for COVID 19 (BATIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04401410
Recruitment Status : Recruiting
First Posted : May 26, 2020
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
AlloVir
Information provided by (Responsible Party):
Premal Lulla, Baylor College of Medicine

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
SARS-CoV 2 Viral Infection COVID 19 Biological: Dose Finding Phase (MTD) Biological: Partially HLA-matched SARS-CoVSTs Other: Routine care (no SARS-CoVSTs) Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BAT IT: Banked Anti-SARS Cov-2 T Cell Infusions for Treatment of COVID 19
Actual Study Start Date : November 4, 2020
Estimated Primary Completion Date : August 15, 2021
Estimated Study Completion Date : August 15, 2021

Arm Intervention/treatment
Experimental: Dose Finding Phase

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: 1x107 cells (flat dose) DL2: 2x107 cells (flat dose) DL3: 4x107 cells (flat dose)

Biological: Dose Finding Phase (MTD)
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.

Experimental: Randomized Pilot - SARS-CoVSTs
Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection.
Biological: Partially HLA-matched SARS-CoVSTs
Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase

Active Comparator: Randomized Pilot - Routine Care
Hospitalized patients with COVID-19 will be treated per current institutional guidelines.
Other: Routine care (no SARS-CoVSTs)
Patients receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).




Primary Outcome Measures :
  1. Dose Escalation Phase: Rate of Dose Limiting Toxicities by CTCAE 5.0 [14 days post infusion] [ Time Frame: 14 days post infusion ]
    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.

  2. 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 ]
    Clinical Response is defined as the proportion of subjects reporting an increase in 2 or more points on the WHO Ordinal Scale. Clinical Response will be measured daily using the WHO Ordinal scale [Scored on a scale from 0 to 8; where 0 = Uninfected and 8 =Dead] or until patient is discharged. The proportion of response in patients in the treatment arm will be compared to the proportion of response in the control arm who have a clinical response by day 7 post-randomization.


Secondary Outcome Measures :
  1. Randomized Trial: Rate of Treatment-related adverse events (tAE) by CTCAE 5.0 [14 days post-randomization] [ Time Frame: 14 days post-randomization ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. SARS-CoV-2 infection confirmed by polymerase chain reaction assay (PCR) from a nasopharyngeal swab or other accepted specimen type. (If testing was performed ≥ 5 days before enrollment, this must be repeated and accept only if positive again).
  2. Currently hospitalized adult patient (≥ 18 years of age) requiring medical care for COVID19
  3. Peripheral oxygen saturation (SpO2) ≥ 92% on room air
  4. Hgb ≥ 7.0 gm/dl
  5. Negative pregnancy test (if applicable)
  6. Patient or parent/guardian capable of providing informed consent (may be obtained electronically)
  7. Evidence of pulmonary infiltrates on chest imaging. Any chest imaging findings which would be consistent with COVID19 would qualify (Eg: ground glass opacities, multifocal infiltrates etc.)
  8. High risk of requiring mechanical ventilation as defined by at least two of the following:

    1. Age ≥ 65 years of age
    2. Hypertension (HTN)
    3. Chronic cardiovascular disease other than HTN (eg: Coronary artery disease, congestive heart failure or cardiomyopathies).
    4. Diabetes Mellitus
    5. Obesity (BMI greater than 35)
    6. Active cancer diagnosis or ongoing (within 3 months) cytotoxic chemo/ radio-therapy for a cancer
    7. Post-hematopoeitic stem cell or solid organ transplantation status
    8. Immunodeficiency states (except those listed as exclusion criteria #1, #7 and #10) as determined by the treating physician (eg: receiving immunosuppressive therapy like rituximab or congenital immunodeficiency syndromes, prior treatment with chemotherapy greater than 3 months ago but per investigators discretion could have lingering effects on the immune system, eg: chemotherapy regimens for lymphomas, ALL or AML etc.)

Exclusion Criteria

  1. Received Anti-thymocyte globulin (ATG), Campath or other T cell immunosuppressive monoclonal antibodies in the 28 days prior to screening for enrollment
  2. Requiring mechanical ventilation at time of T cell infusion
  3. Alanine aminotransferase or aspartate aminotransferase greater than 5 x upper limit of normal
  4. If previously undergone an allogeneic hematopoietic stem cell transplant and have evidence of active acute GVHD greater than or equal to grade 2
  5. Uncontrolled relapse of malignancy
  6. Requiring vasopressors
  7. Evidence of prior HIV infection
  8. Known history of autoimmune disease except prior thyroiditis
  9. Is not suitable at the discretion of the treating physician
  10. Patients on 0.5mg/kg prednisone or equivalent
  11. Greater than grade 1 CRS per American Society for Transplantation and Cellular Therapy (ASTCT) criteria
  12. Patients should not be enrolled on any other interventional clinical trials for COVID19. Patients may receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401410


Contacts
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Contact: Premal Lulla, MD 832-824-4847 lulla@bcm.edu

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Premal Lulla, MD    832-824-4847    lulla@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
AlloVir
Investigators
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Principal Investigator: Premal Lulla Baylor College of Medicine
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Responsible Party: Premal Lulla, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT04401410    
Other Study ID Numbers: H-47739 BAT IT
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Premal Lulla, Baylor College of Medicine:
COVID 19
SARS-CoV 2
Viral infection
Multivirus T cell
Additional relevant MeSH terms:
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Virus Diseases