NCT04578210

Safety Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in COVID-19 pnEumonia or Lymphopenia

A Phase I/II Dose-escalation Multi Center Study to Evaluate the Safety of Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in coronaviruS pnEumonia and/or Lymphopenia

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 84 (actual)
• Sponsor: Instituto de Investigación Hospital Universitario La Paz · Academic / Other
• Sex: All
• Age: 80 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19. Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state. This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.

Detailed description

In this phase I/II trial natural killer (NK) cells or memory T lymphocytes will be infused from donors who have recovered from COVID-19 and have complete resolution of symptoms for at least 14 days. There will be two arms based on the biology of the donor and the patient: Arm 1. Infusion of memory T cells from HLA partially match donors which have the SARS-COV-2 memory T cell repertoire. Arm 2. Infusion of NK cells which are cells of the innate immune system that can eliminate virally infected cells. The investigators expect a quick recovery of the patients with pneumonia or lymphopenia for two reasons: 1. The pool of memory T cells will increase in patients. Memory T cell levels are low in these patients. These lymphocytes have long-life memory, which upon reencountering SARS-CoV-2 will induce enhanced effector function resulting in greater protection of the patient. 2. NK cells act quickly after a viral infection. The number and function of NK cells correlates with the severity of another coronavirus infection, Severe Acute Respiratory Syndrome (SARS), originated in China in 2002. Moreover, the investigators have previous successful experience with other viruses such as CMV, EBV and HHV-6. Patients who have recovered from COVID-19 are the ideal donor candidates because they have immune cells with memory against SARS-CoV-2. Therefore, the infusion of NK and memory T cells from these donors will increase the pool of cells with cytotoxicity to virally infected cells, and will increase the pool of memory cells that respond quicker to a previously encountered stimulus. This will impact in saving thousands of lives, releasing hospital beds, reducing the costs of a national health system and improving the economy of a locked-down country. Cell therapies are safe and cost-effective and successfully used in other diseases. The investigators need new innovative treatments where others have failed. We have performed the phase I: Arm 1.Phase I single-center dose-escalation in 9 patients infused with memory T cells from a HLA partially match convalescent donor. Arm 2. Phase I single-center dose-escalation in 6 patients infused with NK cells from convalescent donors. We evaluate the safety, and feasibility, and obtained the RP2D of a single infusion. We have performed the phase II with memory T cells: The phase II for the infusion of memory T cells from HLA partially match convalescent donors has been carried out. 84 patients have been enrolled and randomized into the SoC treatment or the SoC plus the infusion of memory T cells.

Conditions

• Corona Virus Infection

Interventions

Type	Name	Description
BIOLOGICAL	T memory cells and NK cells	Single infusion of NK or memory T cells from a healthy donor recovered from COVID-19 (dose escalation).

Timeline

• Start date: 2020-09-04
• Primary completion: 2022-01-13
• Completion: 2022-03-30
• First posted: 2020-10-08
• Last updated: 2023-06-01

Locations

1 site across 1 country: Spain