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. 2021 Oct 2;22(1):674.
doi: 10.1186/s13063-021-05625-7.

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 #  1 , P Guerra-García #  1   2   3 , C Ferreras  3 , A M Borobia  1   3   4 , A J Carcas  1   3   4 , J Queiruga-Parada  1 , J L Vicario  5 , I Mirones  2 , C Solano  6 , C Eguizabal  7   8 , B Soria  9   10   11 , A Pérez-Martínez  12   13   14
Affiliations

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 et al. Trials. .

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.

Keywords: Allogeneic; COVID-19; Lymphopenia; Memory T cells; NK cells; Pneumonia; Protocol; Safety.

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Conflict of interest statement

CF, BS, and AP-M filed a patent on this topic. BS received fees from Laminar Pharma, Abbvie, Celgene, Gilead, Sanofi, and Novo-Nordisk not related to this work.

Figures

Fig. 1
Fig. 1
Trial flow chart of the two consecutive phases of the study
See this image and copyright information in PMC

References

    1. World Health Organization. Coronavirus disease 2019 (COVID-19) situation report; data as reported by national authorities by 10AM CET. 03 March 2020.
    1. Jones DS. History in a crisis - lessons for Covid-19. N Engl J Med. 2020;382(18):1681–1683. doi: 10.1056/NEJMp2004361. - DOI - PubMed
    1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0. - DOI - PMC - PubMed
    1. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. Published Online First: 28 February 2020. - PMC - PubMed
    1. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical–therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405–407. doi: 10.1016/j.healun.2020.03.012. - DOI - PMC - PubMed

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