Anti-SARS Cov-2 T Cell Infusions for COVID 19

NCT ID: NCT04401410

Last Updated: 2022-12-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2021-10-12

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.

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.

Conditions

SARS-CoV 2; Viral Infection; COVID 19

Keywords

COVID 19; SARS-CoV 2; Viral infection; Multivirus T cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Dose Finding Phase (MTD)

Intervention Type: BIOLOGICAL

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.

Randomized Pilot - SARS-CoVSTs

Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection.

Group Type: EXPERIMENTAL

Partially HLA-matched SARS-CoVSTs

Intervention Type: BIOLOGICAL

Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase

Randomized Pilot - Routine Care

Hospitalized patients with COVID-19 will be treated per current institutional guidelines.

Group Type: ACTIVE_COMPARATOR

Routine care (no SARS-CoVSTs)

Intervention Type: OTHER

Patients receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).

Interventions

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.

Intervention Type: BIOLOGICAL

Partially HLA-matched SARS-CoVSTs

Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase

Intervention Type: BIOLOGICAL

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).

Intervention Type: OTHER

Eligibility 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). 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

Exclusion Criteria

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).

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Cell and Gene Therapy, Baylor College of Medicine

OTHER

Sponsor Role: collaborator

AlloVir

INDUSTRY

Sponsor Role: collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Premal Lulla

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Premal Lulla

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Houston Methodist Hospital

Houston, Texas, United States

Countries

United States

References

Vasileiou S, Hill L, Kuvalekar M, Workineh AG, Watanabe A, Velazquez Y, Lulla S, Mooney K, Lapteva N, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Eagar TN, Carrum G, Grimes KA, Leen AM, Lulla P. Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients. Haematologica. 2023 Jul 1;108(7):1840-1850. doi: 10.3324/haematol.2022.281946.

Reference Type: DERIVED

PMID: 36373249 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

H-47739 BAT IT

Identifier Type: -

Identifier Source: org_study_id