RECRUITING

T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, phase I dose-escalation study to evaluate the safety of coronavirus-specific T cell (CST) therapy for prevention of SARS-CoV-2 infection in immunocompromised patients following hematopoietic stem cell transplantation (HSCT). Participants will receive donor-derived CSTs for prevention of SARS-CoV-2 infection after HSCT (≥28 days and \<4 months after HSCT). In this dose escalation trial, three doses (1x107/m2, 2x107/m2, and 4x107/m2) will be tested for safety, with study arms for adult (≥18 years of age and \<80 years) HSCT recipients (Arm A) and two arms for pediatric (≥12 years of age and \<18 years; ≥2 years and \<12 years) HSCT recipients (Arm B and Arm C, respectively), and defined dose escalations in each study arm. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.

Official Title

T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients

Quick Facts

Study Start:2021-10-19

Study Completion:2027-12-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05141058

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. For recipient of CSTs derived from an HSCT donor under Arm A: 2. For recipient of CSTs derived from an HSCT donor under Arms B and C: 3. Have evidence of primary engraftment following HSCT (defined by ANC ≥500/mm3 for three consecutive measurements on different days, respectively) 4. Participants receiving calcineurin inhibitors for treatment of GVHD, or for other reasons, should not have any dosage changes within 7 days prior to infusion\\ 5. Karnofsky/Lansky score \>70. 6. ≥2 years to \<80 years of age at enrollment. 7. Absolute neutrophil count (ANC) ≥500/ul. 8. Hemoglobin ≥8.0g/dl (level can be achieved with transfusion). 9. Platelets ≥20 K/ul (level can be achieved with transfusion)\*. 10. Bilirubin ≤2x upper limit normal. 11. Aspartate transaminase (AST) ≤2.5x upper limit of normal. 12. Alanine transaminase (ALT) ≤2.5x upper limit of normal. 13. Estimated GFR \>60mL/min/1.73m2 (calculated per institutional standards). 14. Pulse oximetry of ≥92% on room air for at least 7 days prior to infusion. 15. Age appropriate mean arterial pressure without the use of vasopressors. 16. Negative pregnancy test in female participant of childbearing potential. 17. Male and female participants of childbearing potential must use highly effective birth control measures or practice abstinence for a minimum of 6 months after receiving study therapy 18. Written informed consent and/or signed assent line from participant, parent or guardian.	1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to CST infusion, including ATG, Alemtuzumab, Basiliximab, Tociluzimab, Brentuximab, or other medications under this category as determined by the investigators. 2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to CST infusion. 3. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to CST infusion. 4. Participants with uncontrolled or progressing infections or active infections causing fever (temperature ≥38.1°C). Uncontrolled infections are defined as bacterial, fungal, or viral infections (including HIV and Hepatitis B and C) with either clinical signs of worsening despite standard therapy that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. 1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to CST infusion. 2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to CST infusion. 5. Participants with unexplained fever (temperature ≥38.1°C) within 7 days prior to CST infusion. 6. Participants with evidence of active SARS-CoV-2 infection based on SARS-CoV-2 RT-PCR positivity. 7. Participants with hypotension (mean arterial pressure \<50mmHg in participants \<5 years of age, \<55 mmHg in participants ≥5 and \<14 years of age or \<60 mmHg in participants ≥14 years of age). 8. Participants with pulse pressure \>40 mmHg. 9. Participants with respiratory rate \>20 breaths per minute. 10. Participants with heart rate ≥140 beats per minute. 11. Participants with uncontrolled hypertension as defined by systolic blood pressure \>99th percentile for age (participants \<18 years), and systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg (participants ≥18 years). 12. Participants with metabolic instability. 13. Pediatric participants with modified Ross heart failure Class II disease and adult participants with NYHA Class II disease. 14. Participants with advanced pulmonary disease as defined by requirement for supplemental oxygen or positive pressure ventilation due to pulmonary disease. (This includes participants with active interstitial lung disease (ILD)/pneumonitis, advanced pulmonary disease, a history of ILD/pneumonitis requiring treatment with systemic steroids or a baseline oxygen requirement). 15. Participants with neurological or psychiatric disorders that would, in the opinion of the investigators, place them at increased risk of harm, impact the investigator's abilities to screen for adverse events in the subject, or impair the subject's ability to provide informed consent. 16. Participants receiving checkpoint inhibitors within the previous 3 months prior to CST infusion, including nivolumimab, pembroluzimab, or other related medications. 17. Participants with proven or suspected MIS (in both adults and children) based on the CDC definition and investigator judgement. 18. Participants who are breastfeeding. 19. Participants who have received live vaccines within 30 days, or any SARS-CoV-2 vaccine in the past 28 days prior to enrollment. 20. Participants with any other unrelated medical conditions that would impact the participant's safety in the opinions of the investigators. 21. Participants anticipated to need a blood transfusion within 48 hours of CST infusion. 22. Participants unwilling to utilize effective contraception during the study period (if applicable)

Inclusion Criteria

Exclusion Criteria

1. For recipient of CSTs derived from an HSCT donor under Arm A:
2. For recipient of CSTs derived from an HSCT donor under Arms B and C:
3. Have evidence of primary engraftment following HSCT (defined by ANC ≥500/mm3 for three consecutive measurements on different days, respectively)
4. Participants receiving calcineurin inhibitors for treatment of GVHD, or for other reasons, should not have any dosage changes within 7 days prior to infusion\*\*
5. Karnofsky/Lansky score \>70.
6. ≥2 years to \<80 years of age at enrollment.
7. Absolute neutrophil count (ANC) ≥500/ul.
8. Hemoglobin ≥8.0g/dl (level can be achieved with transfusion).
9. Platelets ≥20 K/ul (level can be achieved with transfusion)\*.
10. Bilirubin ≤2x upper limit normal.
11. Aspartate transaminase (AST) ≤2.5x upper limit of normal.
12. Alanine transaminase (ALT) ≤2.5x upper limit of normal.
13. Estimated GFR \>60mL/min/1.73m2 (calculated per institutional standards).
14. Pulse oximetry of ≥92% on room air for at least 7 days prior to infusion.
15. Age appropriate mean arterial pressure without the use of vasopressors.
16. Negative pregnancy test in female participant of childbearing potential.
17. Male and female participants of childbearing potential must use highly effective birth control measures or practice abstinence for a minimum of 6 months after receiving study therapy
18. Written informed consent and/or signed assent line from participant, parent or guardian.

1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to CST infusion, including ATG, Alemtuzumab, Basiliximab, Tociluzimab, Brentuximab, or other medications under this category as determined by the investigators.
2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to CST infusion.
3. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to CST infusion.
4. Participants with uncontrolled or progressing infections or active infections causing fever (temperature ≥38.1°C). Uncontrolled infections are defined as bacterial, fungal, or viral infections (including HIV and Hepatitis B and C) with either clinical signs of worsening despite standard therapy that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection.
1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to CST infusion.
2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to CST infusion.
5. Participants with unexplained fever (temperature ≥38.1°C) within 7 days prior to CST infusion.
6. Participants with evidence of active SARS-CoV-2 infection based on SARS-CoV-2 RT-PCR positivity.
7. Participants with hypotension (mean arterial pressure \<50mmHg in participants \<5 years of age, \<55 mmHg in participants ≥5 and \<14 years of age or \<60 mmHg in participants ≥14 years of age).
8. Participants with pulse pressure \>40 mmHg.
9. Participants with respiratory rate \>20 breaths per minute.
10. Participants with heart rate ≥140 beats per minute.
11. Participants with uncontrolled hypertension as defined by systolic blood pressure \>99th percentile for age (participants \<18 years), and systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg (participants ≥18 years).
12. Participants with metabolic instability.
13. Pediatric participants with modified Ross heart failure Class II disease and adult participants with NYHA Class II disease.
14. Participants with advanced pulmonary disease as defined by requirement for supplemental oxygen or positive pressure ventilation due to pulmonary disease. (This includes participants with active interstitial lung disease (ILD)/pneumonitis, advanced pulmonary disease, a history of ILD/pneumonitis requiring treatment with systemic steroids or a baseline oxygen requirement).
15. Participants with neurological or psychiatric disorders that would, in the opinion of the investigators, place them at increased risk of harm, impact the investigator's abilities to screen for adverse events in the subject, or impair the subject's ability to provide informed consent.
16. Participants receiving checkpoint inhibitors within the previous 3 months prior to CST infusion, including nivolumimab, pembroluzimab, or other related medications.
17. Participants with proven or suspected MIS (in both adults and children) based on the CDC definition and investigator judgement.
18. Participants who are breastfeeding.
19. Participants who have received live vaccines within 30 days, or any SARS-CoV-2 vaccine in the past 28 days prior to enrollment.
20. Participants with any other unrelated medical conditions that would impact the participant's safety in the opinions of the investigators.
21. Participants anticipated to need a blood transfusion within 48 hours of CST infusion.
22. Participants unwilling to utilize effective contraception during the study period (if applicable)

Contacts and Locations

Study Contact

Susan Conway, MD

CONTACT

202-476-5845

sconway@childrensnational.org

Fahmida Hoq, MBBS

CONTACT

202-476-3634

fhoq@childrensnational.org

Study Locations (Sites)

Children's National Hospital

Washington D.C., District of Columbia, 20010

United States

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University

Baltimore, Maryland, 21287

United States

Collaborators and Investigators

Sponsor: Children's National Research Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-10-19

Study Completion Date2027-12-15

Study Record Updates

Study Start Date2021-10-19

Study Completion Date2027-12-15

Terms related to this study

Additional Relevant MeSH Terms

SARS-CoV-2 Infection