Anti-SARS Cov-2 T Cell Infusions for COVID 19
Anti-SARS Cov-2 T Cell Infusions for COVID 19
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.
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). Date
 of COVID test must be ≤ 5 days prior to infusion.

 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 ≥ 60 years of age

 2. Age ≥ 75 years of age (counts as meeting two criteria)

 3. Hypertension (HTN)

 4. Chronic cardiovascular disease other than HTN (eg: Coronary artery disease,
 congestive heart failure or cardiomyopathies).

 5. Diabetes Mellitus

 6. Obesity (BMI ≥ 30)

 7. Obesity (BMI ≥ 40, counts as meeting two criteria)

 8. Active cancer diagnosis or ongoing (within 3 months) cytotoxic chemo/
 radio-therapy for a cancer

 9. Post-hematopoeitic stem cell or solid organ transplantation status

 10. Immunodeficiency states including HIV infection on antiretroviral therapy (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.)

 11. Chronic obstructive pulmonary disease (COPD)

 12. Current everyday smoker

 13. Chronic kidney disease (eGFR < 30 mL/min/1.73 m2 )

 14. Bronchial asthma (on active treatment prior to admission, eg. Use of rescue
 inhalers or inhaled corticosteroids or other treatments to prevent/treat
 attacks).

 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. Known history of autoimmune disease except prior thyroiditis

 8. Is not suitable at the discretion of the treating physician

 9. Patients on greater than 6mg/day of dexamethasone (IV) or equivalent

 10. Greater than grade 1 CRS per American Society for Transplantation and Cellular Therapy
 (ASTCT) criteria

 11. 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).