Viral Specific T Cell Therapy for COVID-19 Related Pneumonia

NCT ID: NCT04742595

Last Updated: 2024-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-18
• Study Completion Date: 2024-09-20

Brief Summary

This early phase I trial identifies the feasibility, possible benefits and/or side effects of administering SARS-CoV-2 specific cytotoxic T lymphocytes (CTLs) in treating cancer patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus responsible for coronavirus disease 2019 (COVID-19). SARS-CoV-2 Specific CTLs are a type of immune cells that are made from donated blood cells grown in the laboratory and are designed to kill cells infected with SARS-CoV-2 virus. Giving CTLs may help control the COVID-19 in cancer patients.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) specific T cell lines generated by ex vivo expansion as therapy of COVID19 pneumonia in cancer patients.

SECONDARY OBJECTIVES:

I. To obtain preliminary data about the efficacy of administering most closely HLA-matched SARS-COV-2 specific T cell lines generated by ex vivo expansion.

II. To assess the persistence of the administered cells in the patients.

OUTLINE:

Patients receive SARS-COV-2 specific cytotoxic T lymphocytes intravenously (IV) over 30 minutes on day 1. Treatment may repeat every 14 days at investigators' discretion if patient fails to respond, the infection reoccurs, until the viral load becomes negative or until complete resolution of clinical and radiological signs.

After completion of study treatment, patients are followed up at 7, 14, 21, 28, and 45 days, and 3 months after each cytotoxic T lymphocyte infusion.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Symptomatic COVID-19 Infection Laboratory-Confirmed

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (SARS-COV-2 specific cytotoxic T cells)

Patients receive SARS-COV-2 specific cytotoxic T lymphocytes IV over 30 minutes on day 1. Treatment may repeat every 14 days at investigators' discretion if patient fails to respond, the infection reoccurs, until the viral load becomes negative or until complete resolution of clinical and radiological signs.

Group Type: EXPERIMENTAL

SARS-CoV-2 Antigen-specific Cytotoxic T-lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Interventions

SARS-CoV-2 Antigen-specific Cytotoxic T-lymphocytes

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

SARS-CoV-2 Antigen-specific CTLs; SARS-CoV-2 Antigen-specific Cytotoxic T Lymphocytes; SARS-CoV-2-specific Cytotoxic T-lymphocytes

Eligibility Criteria

Inclusion Criteria

Immunocompromised patients with hematological malignances and diagnosis of COVID-19 > 3 weeks prior to study entry, treated with at least one SOC therapy (i.e., remdesivir, monoclonal antibody [bebtelovimab or newer one], paxlovid, molnupiravir, corticosteroids, other EUA or FDA-approved therapies) with progression of symptoms in the following 14 days after treatment started, of at least 1 category on the 8 ordinal category on the 8 ordinal category WHO scale, or CT chest/CXR shows progression of pneumonia or increase oxygen requirements of at least 2 liters from baseline. Patients should not show signs of improvement before enrollment.

• World health organization (WHO) scale:

1. Not hospitalized and no COVID-19 related symptoms;

2. Not hospitalized, with COVID-19 related symptoms;

3. Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control or other nonmedical reasons);

4. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to COVID-19);

5. Hospitalized, requiring any supplemental oxygen by nasal cannula;

6. Hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices;

7. Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and

8. Death.

Immunocompromised patient with hematological malignances is defined as:

• Recipients of an allogeneic stem cell transplantation or other form of cell therapy, for example CAR T-cell therapy
• Patients with hematological malignancies who have been in MRD-negative CR for less than 3 years from the completion of their last treatment.
• Patients with hematological malignancies who have been in MRD-negative CR for more than 3 years from the completion of their last therapy and have a peripheral blood CD4 count <200x109cells/liter
• Patients with hematological malignances who are not in MRD-negative CR and are not expected to require anticancer treatment for at least 28 days after the CTLs infusion.

English and non-English speaking patients. Written informed consent and/or signed assent from patient, parent or guardian. Negative pregnancy test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.

Willingness to comply with the study protocol requirements.

Exclusion Criteria

• Patients receiving systemic steroids at time of enrollment (physiological substitutive therapy s allowed), or who have received ATG --within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment.
• Patients with other infections other than COVID-19
• Active acute or chronic GVHD.
• Patients receiving immunosuppressive therapy
• Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.

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

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Marin, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2020-13875

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-0759

Identifier Type: OTHER

Identifier Source: secondary_id

2020-0759

Identifier Type: -

Identifier Source: org_study_id