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

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)

Overview

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.

Interventions

• 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.

Primary outcome measures

• Incidence of adverse events [Time frame: 12 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• New York Medical College — Valhalla
• Nationwide Children's Hosptial — Columbus
• Children's Hospital of Pennsylvania — Philadelphia
• Medical College of Wisconsin/Children's Hospital of Wisconsin — Milwaukee

Publications

• Chu Y, Milner J, Lamb M, Maryamchik E, Rigot O, Ayello J, Harrison L, Shaw R, Behbehani GK, Mardis ER, Miller K, Prakruthi Rao Venkata L, Chang H, Lee D, Rosenthal E, Kadauke S, Bunin N, Talano JA, Johnson B, Wang Y, Cairo MS. Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. J Infect Dis. 2023 Mar 28;227(6):788-799. doi: 10.1093/infdis/j PMID 36583990

Identifiers

NCT: NCT04896606 · NYMC 604

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗