Trials (Oct 2021)

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: RELEASE study protocol

  • I. García-García,
  • P. Guerra-García,
  • C. Ferreras,
  • A. M. Borobia,
  • A. J. Carcas,
  • J. Queiruga-Parada,
  • J. L. Vicario,
  • I. Mirones,
  • C. Solano,
  • C. Eguizabal,
  • B. Soria,
  • A. Pérez-Martínez

DOI
https://doi.org/10.1186/s13063-021-05625-7
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 12

Abstract

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Abstract Background Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state. This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19. Methods In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC. In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC. Discussion We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. Trial registration ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020

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