SARS-CoV-2 CTLS for Mild to Moderate COVID-19 Disease

Covid19 Clinical Trial

Official title:

A Pilot Study of SARS-CoV-2 Specific Cytotoxic T Lymphocytes (SARS-CoV-2-CTLs) for Treatment of Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04896606
• Other study ID #: NYMC 604
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 20, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: New York Medical College
• Contact: Mitchell S Cairo, MD
• Phone: 9145942150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The 2019 Severe Acute Respiratory Syndrome (SARS) is a global pandemic secondary to a novel coronavirus - SARS-CoV-2. The reported case-fatality ratio for SARS-CoV-2 in the United States is 1.8% with a current death toll of >300,000 and climbing.4 There is no accepted standard of care or FDA approved therapies for treatment of COVID-19. Virus specific cytotoxic T lymphocytes (CTLs) have become an important part of the treatment landscape for viral reactivation post hematopoietic and solid organ transplantation. Donor derived CTLs have been shown to be safe and effective against a variety of viruses including CMV, EBV, BK and adenovirus. We hypothesize that SARS-CoV-2 specific CTLs generated from a previously infected family donor will be safe and effective for treatment of COVID-19 in family members with mild to moderate disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

INCLUSION CRITERIA

• Age =18 to 65 years. AND

• Proven infection with SARS-CoV-2, defined as detection of SARS-CoV-2 by RT-PCR from nasopharyngeal swab or lower respiratory tract specimen AND

• Hospitalized at the time of enrollment AND

• HLA Matched Family Related donor with recent SARS-CoV-2 infection is at least 10 days out from symptom onset. A negative result for COVID-19 by a diagnostic test is not necessary to qualify the donor AND

• In Stage I or II of disease (mild or moderate) at the time of enrollment (Table 1) AND

• ONE of the following high-risk conditions:

• Chronic lung disease not requiring oxygen at home prior to admission (including but not limited to COPD, cystic fibrosis, asthma and sickle cell disease); Underlying heart disease (including hypertension); Patients with an acute myocardial infarction within the last 3 months will require cardiology clearance prior to enrollment; Diabetes mellitus (type I or II) ; Obesity (BMI = 30); Immunosuppressed, based on investigator's assessment.

EXCLUSION CRITERIA:

• Stage III disease (severe) at the time of enrollment (see Table 1)

• Lack of an identified eligible HLA family related donor

• No high-risk comorbidities defined in the inclusion criteria (Section 5.1)

• Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of enrollment

• Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL Infusion

• Patients with chronic respiratory failure requiring ventilator support and/or oxygen at home prior to admission are excluded

• Patients with stage D heart failure and/or symptoms at rest are excluded

• Renal function: patients with eGFR or CrCl <30 mL/min/1.73 m2 will be excluded from study entry.

• Liver function: Total bilirubin > 2 mg/dl (unless Gilbert's syndrome) OR ALT/AST > 5 x ULN

• Patients currently listed for transplant or potentially eligible to receive organ transplants are excluded from this study

• Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients =16 years) score =50%

• Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment and for at least 6 weeks after the last dose of SARS-CoV-2 CTLS.

• Male subjects with female partners of childbearing age who are not willing to use an effective method of birth control during study treatment and for at least 6 weeks after the last dose of SARS-CoV-2 CTLS.

• Concurrent use of following medications is prohibited:

• Steroids (>2 mg/kg/day prednisone equivalent); Immunotherapies within 4 weeks prior to CTL infusion including checkpoint blockade, ATG, Campath, CAR T cells, blinatumomab; Chemotherapy: Tyrosine kinase inhibitors and hydroxyurea must be stopped > 72 hours prior to SARS-COV-2-CTL cell infusion; High dose chemotherapy must be stopped > 2 weeks prior to SARS-CoV-2-CTLs. High dose chemotherapy is defined in this protocol as any cancer directed therapy causing myelosuppression; Pegylated-asparaginase must be stopped > 4 weeks prior to SARS-COV-2-CTL infusion; Intrathecal chemotherapy must be stopped > 1 week prior to SARS-COV-2-CTL infusion (e.g. intrathecal methotrexate); Anti T-cell Antibodies: Administration of any T cell lytic or toxic antibody (e.g. alemtuzumab) within 30 days prior to SARS-CoV-2-CTLs is prohibited.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Other:
• Standard of Care
Patients will receive standard of care for COVID-19.

Biological:
• SARS-CoV2-CTLS
Patients may receive up to 5 CTL infusions to treat SARA-CoV-2 in combination with standard of care.

Locations

Country	Name	City	State
United States	Nationwide Children's Hosptial	Columbus	Ohio
United States	Medical College of Wisconsin/Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of Pennsylvania	Philadelphia	Pennsylvania
United States	New York Medical College	Valhalla	New York

Sponsors (4)

Lead Sponsor	Collaborator
New York Medical College	Children's Hospital of Philadelphia, Medical College of Wisconsin, Nationwide Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events	no adverse events will occur due to CTL infusion(s)	12 weeks