Anti-SARS Cov-2 T Cell Infusions for COVID 19
- Conditions
- SARS-CoV 2Viral InfectionCOVID 19
- Interventions
- Biological: Dose Finding Phase (MTD)Biological: Partially HLA-matched SARS-CoVSTsOther: Routine care (no SARS-CoVSTs)
- Registration Number
- NCT04401410
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Finding Phase Dose Finding Phase (MTD) 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) Randomized Pilot - SARS-CoVSTs Partially HLA-matched SARS-CoVSTs Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection. Randomized Pilot - Routine Care Routine care (no SARS-CoVSTs) Hospitalized patients with COVID-19 will be treated per current institutional guidelines.
- Primary Outcome Measures
Name Time Method Randomized Trial: Rate of Clinical Response as assessed by the World Health Organization (WHO) Ordinal Scale [7 days post-randomization or hospital discharge] 7 Days post-randomization or at time of hospital discharge 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.
Dose Escalation Phase: Rate of Dose Limiting Toxicities by CTCAE 5.0 [14 days post infusion] 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.
- Secondary Outcome Measures
Name Time Method Randomized Trial: Rate of Treatment-related adverse events (tAE) by CTCAE 5.0 [14 days post-randomization] 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.
Trial Locations
- Locations (1)
Houston Methodist Hospital
🇺🇸Houston, Texas, United States