Using donor-derived T cells to treat mild to moderate COVID-19

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)

This study is testing whether T cells from family members who have recovered from COVID-19 can help treat hospitalized patients with mild to moderate COVID-19.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: New York Medical College (other)
• Drugs / interventions: blinatumomab, alemtuzumab, CAR T, Chemotherapy, methotrexate, prednisone
• Locations: 4 sites (Valhalla, New York and 3 other locations)
• Trial ID: NCT04896606 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of SARS-CoV-2 specific cytotoxic T lymphocytes (CTLs) derived from family donors who have recovered from COVID-19 to treat family members with mild to moderate disease. Participants must be hospitalized and have a confirmed SARS-CoV-2 infection, with specific eligibility criteria including age and underlying health conditions. The study aims to assess the safety and effectiveness of these CTLs as a potential treatment option for COVID-19, where no standard therapies currently exist.

Who should consider this trial

Good fit: Ideal candidates are hospitalized individuals aged 18 to 65 with a confirmed SARS-CoV-2 infection and specific high-risk health conditions.

Not a fit: Patients with severe COVID-19 disease or those without a suitable family donor may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel treatment option for patients with mild to moderate COVID-19, potentially improving recovery outcomes.

How similar studies have performed: While the use of CTLs for viral infections has shown promise in other contexts, this specific application for COVID-19 is novel and has not been extensively tested.

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.

Where this trial is running

Valhalla, New York and 3 other locations

• New York Medical College — Valhalla, New York, United States (RECRUITING)
• Nationwide Children's Hosptial — Columbus, Ohio, United States (NOT_YET_RECRUITING)
• Children's Hospital of Pennsylvania — Philadelphia, Pennsylvania, United States (NOT_YET_RECRUITING)
• Medical College of Wisconsin/Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Mitchell S Cairo, MD

Conditions: Covid19