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.
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.
Biological: SARS-CoV-2 Antigen-specific Cytotoxic T-lymphocytes
Given IV
Other Name: Array
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
M D Anderson Cancer Center
Houston, Texas, United States
Investigator: David Marin, MD
Contact: 713-792-4179
dmarin@mdanderson.org
Investigator: Katy Rezvani, MD
David Marin, MD
713-792-4179
dmarin@mdanderson.org
David Marin, MD, Principal Investigator
M.D. Anderson Cancer Center