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

NCT ID: NCT04896606

Last Updated: 2023-10-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-20
• Study Completion Date: 2025-12-31

Brief 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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SARS-CoV-2 CTLS + Standard of Care

Patients will get family donor derived SARS-CoV-2 cytotoxic t-lymphocytes up to 5 times every 2 weeks along with Standard of care of COVID-19.

Group Type: EXPERIMENTAL

Standard of Care

Intervention Type: OTHER

Patients will receive standard of care for COVID-19.

SARS-CoV2-CTLS

Intervention Type: BIOLOGICAL

Patients may receive up to 5 CTL infusions to treat SARA-CoV-2 in combination with standard of care.

Standard of Care Only

Patients will NOT received COVID CTLs but will get standard of care.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

Patients will receive standard of care for COVID-19.

Interventions

Standard of Care

Patients will receive standard of care for COVID-19.

Intervention Type: OTHER

SARS-CoV2-CTLS

Patients may receive up to 5 CTL infusions to treat SARA-CoV-2 in combination with standard of care.

Intervention Type: BIOLOGICAL

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.

• 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.

Exclusion Criteria

• Stage III disease (severe) at the time of enrollment (see Table 1)
• Lack of an identified eligible HLA family related donor

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: collaborator

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitchell S Cairo, MD

Role: STUDY_CHAIR

New York Medical College

Locations

New York Medical College

Valhalla, New York, United States

Site Status: RECRUITING

Nationwide Children's Hosptial

Columbus, Ohio, United States

Site Status: NOT_YET_RECRUITING

Children's Hospital of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: NOT_YET_RECRUITING

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Mitchell S Cairo, MD

Role: CONTACT

mitchell_cairo@nymc.edu

9145942150

Lauren Harrison, RN, MSN

Role: CONTACT

lauren_harrison@nymc.edu

16172857844

Facility Contacts

Lauren Harrison, MSN, RN

Role: primary

lauren_harrison@nymc.edu

617-285-7844

Elizabeth Mintzer

Role: backup

emintzer2@nymc.edu

Dean Lee, MD, PhD

Role: primary

Dean.Lee@nationwidechildrens.org

614-722-3550

Nancy Bunin, MD

Role: primary

buninn@email.chop.edu

215-590-2255

Julie A Talano, MD

Role: primary

jtalano@mcw.edu

414-955-4185

Kathy Jodarski

Role: backup

kjodarski@chw.org

414-266-2681

References

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/jiac500.

Reference Type: DERIVED

PMID: 36583990 (View on PubMed)

Other Identifiers

NYMC 604

Identifier Type: -

Identifier Source: org_study_id