Covid19Phase 1NCT04765449
Transfer of Infection Fighting Immune Cells Generated in the Laboratory to High Risk Patients With COVID-19 Infection
A Phase 1 study testing Cytotoxic T Lymphocytes in people with Covid19, run by Thomas Jefferson University at 1 site in United States.
Trial summary
This clinical trial will study the safety and efficacy of COVID-19-specific T cells when given as treatment to adult patients (age ≥ 18 years) with a COVID-19 infection. This immunologic treatment is aimed at patients, who are at high risk of progression due to their advanced age, or other underlying health… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Cytotoxic T Lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2021to 19 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a documented active COVID-19 infection and one of the following high-risk criteria:
- Malignancy receiving radiation or chemotherapy in the prior 24 months.
- Chronic lung disease such as asthma, COPD, interstitial lung disease, pulmonary hypertension or cystic fibrosis, requiring treatment beyond inhaled medications
- Hypertension either treated or with evidence of need for treatment
- Cardiovascular disease requiring active medical monitoring and care including heart failure, heart dysrhythmias, coronary artery disease, congenital heart disease, cardiomyopathy, or pulmonary hypertension
- History of ischemic stroke
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- Diabetes (type 1, type 2, or gestational) requiring treatment with insulin or oral hypoglycemics
- Chronic Kidney Disease (Hx of stage 3b or greater as defined by the National Kidney Foundation)
- Chronic Liver Disease (Previously diagnosed with cirrhosis or previously classified as having Pugh-Child class A-C liver disease) oObesity (BMI >= 35) oSickle Cell Disease or Thalassemia
- Patients requiring nursing home support or who have a Karnofsky Performance Status of 70% or less antedating their COVID-19 illness.
- Age >= 65 (with or without previously identified comorbid conditions)
Who cannot join
- Matching their intended CTL product donor at 5 or 6 of 6 HLA-class I (HLA-A, B, and C) alleles.
- Requiring supplemental oxygen
- Evidence of active COVID-19-related CRS as evidenced by 2 or more of the following characteristics of cytokine storm:
- o> grade 1 CRS on ASTCT criteria. ASTCT criteria do not provide quantitative guidelines regarding the definition of hypotension. For this trial, hypotension will be defined as:
- requiring vasopressors
- Systolic blood pressure <90 mm Hg
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- Diastolic B/P < 60 mm Hg NB Lower systolic and diastolic blood pressures will be acceptable if patient's blood pressure is at his/her known baseline.
- Uncontrolled hypertension as defined by a systolic pressure of > 180 mm Hg or diastolic pressure > 100 mm Hg. A second blood pressure reading may be obtained by study personnel to assure blood pressure accuracy.
- radiographic studies consistent with adult respiratory distress syndrome
- Patients requiring acute dialysis
- hyperferritinemia as defined by ferritin > 2000 ng/mL 55
- Concurrent treatment with >5 mg of prednisone daily (or equivalent).
- Current or ongoing administration of calcineurin inhibitors, chemotherapy, radiation, or other immunosuppressive agents.
- That cannot be held for 14 days after CTL infusion
- That would not decay 3 1/2 half-lives by the day of CTL infusion using longest published half-life.
- Receipt of agents with ongoing immunosuppressive properties in the last 30 days including, ATG, Alemtuzumab, or similar agents.
- Prior allogeneic bone marrow, stem cell, or solid organ transplant. Patients with a history of autologous transplant are eligible for study if one year has elapsed since their transplant.
- Active HIV infection with CD4 count less than 200/ul.
- Pregnancy (lactating females allowable)
- Concomitant treatment with another experimental intervention for COVID-19 other than Remdesivir.
- History of allergic reaction to cellular therapy products (includes blood transfusion), diphenhydramine, or tocilizumb
- Corrected QT interval > 450 milliseconds
- History of torsade de pointes or other ventricular arrhythmia Women of childbearing potential, and partners of women of childbearing potential should be using at least one method of highly effective contraception at the time of enrollment and for the 14-day duration of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: Third-Party COVID-19-Specific Cytotoxic T Lymphocytes for the Treatment of Elderly and High-Risk Patients With COVID-19 Infection
This clinical trial will study the safety and efficacy of COVID-19-specific T cells when given as treatment to adult patients (age ≥ 18 years) with a COVID-19 infection. This immunologic treatment is aimed at patients, who are at high risk of progression due to their advanced age, or other underlying health conditions. The outcomes of patients receiving the T cells (Arm A) will be compared to patients treated with standard of care (Arm B).
Read the detailed description
T cells that recognize COVID-19 peptides will be manufactured at Thomas Jefferson University and are frozen and ready for use. The T cells have to have an immune protein called HLA in common with a patient to work. If a patient enrolled on the COVID-19 study has this HLA, they will receive a dose of the COVID-19 T cells. Groups of 3-6 patients will be treated at each testing dose level. There are four dose levels of T cells: 1 x 105/kg, 3 x 105/kg, 1 x 106/kg, and 3 x 106/kg. Patients will receive the T cells intravenously in the hospital and be monitored there for 4 days before being discharged. Before discharge, patients will be taught to take and record their temperature, blood pressure, and oxygen levels (using a finger monitor) at home. After discharge, study staff will continue to monitor patient symptoms and recordings with video visits or phone calls daily until the monitoring period of 14 days is over. Patients will also be asked to give blood samples 7, 14, 28, days and 2, 3, and 6 months after the T cells are given. Patients who meet study criteria and wish to participate but do not have the HLA protein in common with the T cells, will be monitored by study personnel in their own homes for the full 14 day period. These patients will also be taught to take and record their temperature, blood pressure, and oxygen level. Study personnel will contact them daily by video or voice calls and check on the results of their readings and their symptoms. These patients may be treated with any standard or experimental COVID-19 therapy. How patients handle their COVID-19 infection will be compared between the group of people receiving the T cells and the group of people who do not receive the T cells.
- Conditions
- Covid19
- Being tested
- Cytotoxic T Lymphocytes
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytotoxic T LymphocytesDrug
Also called CTLs
Given IV. Cytotoxic T Lymphocytes collected from healthy volunteer donors who have recovered from COVID-19. The T cells are collected, manufactured to be COVID-specific, and stored frozen at Thomas Jefferson University.
| Study group | Role | What they receive |
|---|---|---|
| ARM A: Covid-19 Patients Receiving CTLs | Experimental | Patients who have an HLA antigen in common with COVID-19 fighting T cells will receive the COVID-19 T cells. They will be premedicated with diphenhydramine and acetaminophen before the cells are infused intravenously. Close monitoring will continue in the patients' homes for 14 days. Three to six patients will receive a specific dose of T cells, and then if there are no serious side effects, the dose will be increased for the next group of patients. There are 4 doses of T cells to be tested, and each patient will complete a 14 day monitoring period before the next patient can be treated. Receives: Drug: Cytotoxic T Lymphocytes |
| ARM B: Covid-19 Patients Not Receiving CTLs | No intervention | Patients in the observation arm will not have inherited an HLA antigen in common with the COVID-19 T cells and so cannot receive the T cells. They will be monitored by the study staff for the 14 day monitoring period in their homes. They will be taught to record their own blood pressure, temperature, and oxygen level (pulse oximetry) at home and report this information, as well as their progress in getting over the COVID-19 infection, to the study staff every day by phone. The outcomes of patients on arm B will be compared to the outcomes of patients treated on Arm A to see if the T cells made a difference in how patients recovered from COVID-19. Patients in Arm B are not prevented from being treated with any available COVID-19 therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of COVID-19-specific CTLs: Infusion Reactions
Safety will be measured by the absence of: Grade ≥ 3 acute infusion reactions
Measured: Within 48 Hours of CTL Infusion
Safety of COVID-19-specific CTLs: Grade 4 AEs
Safety will be measured by the absence of: Any grade 4 or higher adverse event thought to be related to the CTL therapy and outside the spectrum of identified COVID related events.
Measured: Within 14 days of CTL infusion
Safety of COVID-19-specific CTLs: GVHD
Safety will be measured by the absence of: Any manifestation of acute GVHD (for acute grades 2-4 GVHD-Glucksberg criteria) 53 resistant to 2 mg/kg of solumedrol or equivalent
Measured: Within 14 days of CTL infusion
Safety of COVID-19-specific CTLs: Marrow Aplasia
Safety will be measured by the absence of: Marrow aplasia due to 3rd party engraftment
Measured: Within 14 days of CTL infusion
Safety of COVID-19-specific CTLs: Neurotoxicty
Safety will be measured by the absence of: Grade ≥ 2+ Neurotoxicity as measured by the ASTCT/ICANS consensus grading system
Measured: Within 14 days of CTL infusion
Safety of COVID-19-specific CTLs: CRS
Safety will be measured by the absence of: Grade ≥ 2+ CRS as measured by the ASTCT Consensus Grading Criteria for CRS
Measured: Within 14 days of CTL infusion
Secondary outcomes (5)
Measurement of COVID-19 viral load
Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected
Measured: Up to 14 Days
Studies to detect the persistence of the COVID-19-specific T cells after COVID-19 T cell infusion
Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected
Measured: Up to 6 months
Studies to examine the development of endogenous COVID-19 specific T cells
Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected
Measured: Up to 6 months
Studies to examine the development of anti-COVID-19 antibodies
Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected
Measured: Up to 6 months
Review of medical history including the need for supplemental oxygen, the ability to return to work, performance status, grade of dyspnea, grade of fatigue, survival, the need for blood pressure support
Patients will have their medical course followed by the study team
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start15 Sep 2021
- Primary completion29 Jul 2022
- Study completion19 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Tevogen Bio Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04765449
- Sponsor's protocol ID
- 21P.015
- Other IDs
- JT 16697
- Status last verified
- Apr 2025
- First submitted
- 19 Feb 2021
- Last updated
- 29 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grosso D, Wagner JL, O'Connor A, Keck K, Huang Y, Wang ZX, Mehler H, Leiby B, Flomenberg P, Gergis U, Nikbakht N, Morris M, Karp J, Peedin A, Flomenberg N. Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19. Blood Adv. 2024 Aug 13;8(15):4113-4124. doi: 10.1182/bloodadvances.2024013344.
PubMed 38885482
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Third-Party COVID-19-Specific Cytotoxic T Lymphocytes for the Treatment of Elderly and High-Risk Patients With COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04765449
- Acronym / sponsor ID
- 21P.015
- Conditions
- Covid19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Tevogen Bio Inc
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 19 Jan 2023 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will study the safety and efficacy of COVID-19-specific T cells when given as treatment to adult patients (age ≥ 18 years) with a COVID-19 infection. This immunologic treatment is aimed at patients, who are at high risk of progression due to their advanced age, or other underlying health conditions. The outcomes of patients receiving the T cells (Arm A) will be compared to patients treated with standard of care (Arm B).
Detailed description
T cells that recognize COVID-19 peptides will be manufactured at Thomas Jefferson University and are frozen and ready for use. The T cells have to have an immune protein called HLA in common with a patient to work. If a patient enrolled on the COVID-19 study has this HLA, they will receive a dose of the COVID-19 T cells. Groups of 3-6 patients will be treated at each testing dose level. There are four dose levels of T cells: 1 x 105/kg, 3 x 105/kg, 1 x 106/kg, and 3 x 106/kg. Patients will receive the T cells intravenously in the hospital and be monitored there for 4 days before being discharged. Before discharge, patients will be taught to take and record their temperature, blood pressure, and oxygen levels (using a finger monitor) at home. After discharge, study staff will continue to monitor patient symptoms and recordings with video visits or phone calls daily until the monitoring period of 14 days is over. Patients will also be asked to give blood samples 7, 14, 28, days and 2, 3, and 6 months after the T cells are given. Patients who meet study criteria and wish to participate but do not have the HLA protein in common with the T cells, will be monitored by study personnel in their own homes for the full 14 day period. These patients will also be taught to take and record their temperature, blood pressure, and oxygen level. Study personnel will contact them daily by video or voice calls and check on the results of their readings and their symptoms. These patients may be treated with any standard or experimental COVID-19 therapy. How patients handle their COVID-19 infection will be compared between the group of people receiving the T cells and the group of people who do not receive the T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A: Covid-19 Patients Receiving CTLs | Experimental | Drug: Cytotoxic T LymphocytesPatients who have an HLA antigen in common with COVID-19 fighting T cells will receive the COVID-19 T cells. They will be premedicated with diphenhydramine and acetaminophen before the cells are infused intravenously. Close monitoring will continue in the patients' homes for 14 days. Three to six patients will receive a specific dose of T cells, and then if there are no serious side effects, the dose will be increased for the next group of patients. There are 4 doses of T cells to be tested, and each patient will complete a 14 day monitoring period before the next patient can be treated. |
| ARM B: Covid-19 Patients Not Receiving CTLs | No intervention | –Patients in the observation arm will not have inherited an HLA antigen in common with the COVID-19 T cells and so cannot receive the T cells. They will be monitored by the study staff for the 14 day monitoring period in their homes. They will be taught to record their own blood pressure, temperature, and oxygen level (pulse oximetry) at home and report this information, as well as their progress in getting over the COVID-19 infection, to the study staff every day by phone. The outcomes of patients on arm B will be compared to the outcomes of patients treated on Arm A to see if the T cells made a difference in how patients recovered from COVID-19. Patients in Arm B are not prevented from being treated with any available COVID-19 therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Malignancy receiving radiation or chemotherapy in the prior 24 months.
- Chronic lung disease such as asthma, COPD, interstitial lung disease, pulmonary hypertension or cystic fibrosis, requiring treatment beyond inhaled medications
- Hypertension either treated or with evidence of need for treatment
- Cardiovascular disease requiring active medical monitoring and care including heart failure, heart dysrhythmias, coronary artery disease, congenital heart disease, cardiomyopathy, or pulmonary hypertension
- History of ischemic stroke
Key exclusion criteria (23 listed)
- Matching their intended CTL product donor at 5 or 6 of 6 HLA-class I (HLA-A, B, and C) alleles.
- Requiring supplemental oxygen
- Evidence of active COVID-19-related CRS as evidenced by 2 or more of the following characteristics of cytokine storm:
- o> grade 1 CRS on ASTCT criteria. ASTCT criteria do not provide quantitative guidelines regarding the definition of hypotension. For this trial, hypotension will be defined as:
- Current or ongoing administration of calcineurin inhibitors, chemotherapy, radiation, or other immunosuppressive agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytotoxic T LymphocytesAlso: CTLsGiven IV. Cytotoxic T Lymphocytes collected from healthy volunteer donors who have recovered from COVID-19. The T cells are collected, manufactured to be COVID-specific, and stored frozen at Thomas Jefferson University. | Drug | ARM A: Covid-19 Patients Receiving CTLs |
Primary outcome
Safety of COVID-19-specific CTLs: Infusion Reactions
Time frame: Within 48 Hours of CTL Infusion
Safety will be measured by the absence of: Grade ≥ 3 acute infusion reactions
Safety of COVID-19-specific CTLs: Grade 4 AEs
Time frame: Within 14 days of CTL infusion
Safety will be measured by the absence of: Any grade 4 or higher adverse event thought to be related to the CTL therapy and outside the spectrum of identified COVID related events.
Safety of COVID-19-specific CTLs: GVHD
Time frame: Within 14 days of CTL infusion
Safety will be measured by the absence of: Any manifestation of acute GVHD (for acute grades 2-4 GVHD-Glucksberg criteria) 53 resistant to 2 mg/kg of solumedrol or equivalent
Safety of COVID-19-specific CTLs: Marrow Aplasia
Time frame: Within 14 days of CTL infusion
Safety will be measured by the absence of: Marrow aplasia due to 3rd party engraftment
Safety of COVID-19-specific CTLs: Neurotoxicty
Time frame: Within 14 days of CTL infusion
Safety will be measured by the absence of: Grade ≥ 2+ Neurotoxicity as measured by the ASTCT/ICANS consensus grading system
Safety of COVID-19-specific CTLs: CRS
Time frame: Within 14 days of CTL infusion
Safety will be measured by the absence of: Grade ≥ 2+ CRS as measured by the ASTCT Consensus Grading Criteria for CRS
5 secondary outcomes
Measurement of COVID-19 viral load
Time frame: Up to 14 Days
Studies to detect the persistence of the COVID-19-specific T cells after COVID-19 T cell infusion
Time frame: Up to 6 months
Studies to examine the development of endogenous COVID-19 specific T cells
Time frame: Up to 6 months
Studies to examine the development of anti-COVID-19 antibodies
Time frame: Up to 6 months
Review of medical history including the need for supplemental oxygen, the ability to return to work, performance status, grade of dyspnea, grade of fatigue, survival, the need for blood pressure support
Time frame: Up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Derived from this study: PubMed 38885482Grosso D, Wagner JL, O'Connor A, Keck K, Huang Y, Wang ZX, Mehler H, Leiby B, Flomenberg P, Gergis U, Nikbakht N, Morris M, Karp J, Peedin A, Flomenberg N. Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19. Blood Adv. 2024 Aug 13;8(15):4113-4124. doi: 10.1182/bloodadvances.2024013344.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytotoxic T Lymphocytes in people with Covid19, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of COVID-19-specific CTLs: Infusion Reactions (time frame: Within 48 Hours of CTL Infusion). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04765449, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.