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Viral Specific T Cell Therapy for COVID-19 Related Pneumonia

Primary Purpose

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

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Hematopoietic and Lymphoid Cell Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients age 18 years or older with COVID-19 related infection, defined as patients with a positive SARS-CoV-2 positive reverse transcriptase polymerase chain reaction (RT-PCR) test (bronchoalveolar lavage [BAL], nasal or pharyngeal) within 2 weeks of enrollment and respiratory symptoms (e.g., cough, shortness of breath, chest pain, hemoptysis, nasal congestion, rhinorrhea, anosmia).
Immunocompromised patient with cancer defined as:
- Recipients of an stem cell transplantation
- Patients with hematological malignancies who have been in minimal residual disease (MRD)-negative complete remission (CR) for less than 3 years
- Patients with hematological malignances who have received chemotherapy, targeted therapy or immunotherapy within 6 months prior enrollment and who are not planned to receive additional therapy for at least 6 weeks after the infusion. All non-hematological toxicity from prior therapy must have been recovered to grade II or less prior enrollment
- Patients organ solid malignances who have received chemotherapy, targeted therapy or immunotherapy within 6 months prior enrollment and who are not planned to receive additional chemotherapy, targeted therapy or immunotherapy for at least 6 weeks after the infusion. All toxicity from prior therapy must have been recovered to grade II or less prior enrollment
- Patients with hematological malignancies who have been in MRD-negative CR for more than 3 years and have a peripheral blood CD4 count < 200 x 10^9cells/liter
- Patients with organ solid malignancies who received chemotherapy, targeted therapy or immunotherapy more than six months prior enrollment and have a peripheral blood CD4 count < 200 x 10^9cells/liter
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 prednisone > 0.1 mg/kg/day or equivalent at time of enrollment, or who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment
Patients with other uncontrolled infections other than COVID-19: For bacterial infections, patients must be receiving therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
Karnosky < 70 prior to SARS-COV-2 infection
Active acute graft versus host disease (GVHD) grade >= 2
Patients with primary lung cancer not in remission and patients with existing lung metastasis of solid organ tumors

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

Assessment of feasibility

Proportion of patients who receive at least one severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) specific cytotoxic T lymphocytes (CTLs) infusion. Study approach will be considered feasible if at least 50% of the enrolled eligible patients receive one CTLs infusion.

Incidence of adverse events

Will collect adverse events and grade them according to Common Terminology Criteria for Adverse Events version 4.0. Attribution will be assigned based on the relationship to the cell infusion.

Secondary Outcome Measures

Response to cytotoxic T lymphocytes

Defined as extubation for patients who required intubation and mechanical ventilation, reduction in the need of oxygen of 50% or a reduction in the fraction of inspired oxygen (FiO2) below 30% or oxygen discontinuation for patients who are not intubated but require oxygen, or resolution of clinical and radiological signs and symptoms for patients who do not require oxygen. Proportion of patients experiencing response will be computed with associated 95% confidence interval.

Overall survival

Will be estimated using the Kaplan-Meier method.

Relapse free survival (original malignancy)

Will be estimated using the Kaplan-Meier method.

Cumulative incidence of coronavirus disease 2019 pneumonia resolution after therapy

Cumulative incidence of grade 2-4 or 3-4 graft versus host disease (GVHD), and chronic GVHD

Will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.

All-cause mortality

Proportion of subjects alive and free of respiratory failure

Reconstitution of anti-virus immunity

Number of SARS-COV-2 specific T-cells in blood will be determined for each patient.

Full Information

NCT ID

NCT04742595

First Posted

February 3, 2021

Last Updated

September 21, 2023

Sponsor

M.D. Anderson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04742595

Brief Title

Viral Specific T Cell Therapy for COVID-19 Related Pneumonia

Official Title

Administration of Expanded, Most Closely HLA Matched SARS-CoV-2-Specific T Cells for the Treatment of COVID-19 in Patients With Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 18, 2020 (Actual)

Primary Completion Date

March 31, 2024 (Anticipated)

Study Completion Date

March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

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

Other Intervention Name(s)

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

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Assessment of feasibility

Description

Time Frame

Up to 3 months post-infusion

Title

Incidence of adverse events

Description

Will collect adverse events and grade them according to Common Terminology Criteria for Adverse Events version 4.0. Attribution will be assigned based on the relationship to the cell infusion.

Time Frame

Up to 3 months post-infusion

Secondary Outcome Measure Information:

Title

Response to cytotoxic T lymphocytes

Description

Time Frame

Up to 2 weeks post-infusion

Title

Overall survival

Description

Will be estimated using the Kaplan-Meier method.

Time Frame

From treatment start date to date of death, assessed up to 3 months post-infusion

Title

Relapse free survival (original malignancy)

Description

Will be estimated using the Kaplan-Meier method.

Time Frame

From treatment start date to the date of documented disease recurrence or death, assessed up to 3 months post-infusion

Title

Cumulative incidence of coronavirus disease 2019 pneumonia resolution after therapy

Time Frame

Up to 3 months post-infusion

Title

Cumulative incidence of grade 2-4 or 3-4 graft versus host disease (GVHD), and chronic GVHD

Description

Will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.

Time Frame

Up to 3 months post-infusion

Title

All-cause mortality

Time Frame

At 28 days post-infusion

Title

Proportion of subjects alive and free of respiratory failure

Time Frame

At 28 days post-infusion

Title

Reconstitution of anti-virus immunity

Description

Number of SARS-COV-2 specific T-cells in blood will be determined for each patient.

Time Frame

Up to 3 months post-infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients age 18 years or older with COVID-19 related infection, defined as patients with a positive SARS-CoV-2 positive reverse transcriptase polymerase chain reaction (RT-PCR) test (bronchoalveolar lavage [BAL], nasal or pharyngeal) within 2 weeks of enrollment and respiratory symptoms (e.g., cough, shortness of breath, chest pain, hemoptysis, nasal congestion, rhinorrhea, anosmia). Immunocompromised patient with cancer defined as: Recipients of an stem cell transplantation Patients with hematological malignancies who have been in minimal residual disease (MRD)-negative complete remission (CR) for less than 3 years Patients with hematological malignances who have received chemotherapy, targeted therapy or immunotherapy within 6 months prior enrollment and who are not planned to receive additional therapy for at least 6 weeks after the infusion. All non-hematological toxicity from prior therapy must have been recovered to grade II or less prior enrollment Patients organ solid malignances who have received chemotherapy, targeted therapy or immunotherapy within 6 months prior enrollment and who are not planned to receive additional chemotherapy, targeted therapy or immunotherapy for at least 6 weeks after the infusion. All toxicity from prior therapy must have been recovered to grade II or less prior enrollment Patients with hematological malignancies who have been in MRD-negative CR for more than 3 years and have a peripheral blood CD4 count < 200 x 10^9cells/liter Patients with organ solid malignancies who received chemotherapy, targeted therapy or immunotherapy more than six months prior enrollment and have a peripheral blood CD4 count < 200 x 10^9cells/liter 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 prednisone > 0.1 mg/kg/day or equivalent at time of enrollment, or who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment Patients with other uncontrolled infections other than COVID-19: For bacterial infections, patients must be receiving therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection Karnosky < 70 prior to SARS-COV-2 infection Active acute graft versus host disease (GVHD) grade >= 2 Patients with primary lung cancer not in remission and patients with existing lung metastasis of solid organ tumors

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

David Marin, MD

Phone

713-792-4179

dmarin@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Marin, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Marin, MD

Phone

713-792-4179

dmarin@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Katy Rezvani, MD

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

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Viral Specific T Cell Therapy for COVID-19 Related Pneumonia

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