Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

CD45RA(−) memory T cells COVID-19 cell therapy immune recovery lymphopenia viral diseases

Journal

Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309

Informations de publication

Date de publication:
29 Oct 2023
Historique:
received: 11 06 2023
revised: 05 09 2023
accepted: 05 10 2023
pubmed: 29 10 2023
medline: 29 10 2023
entrez: 28 10 2023
Statut: aheadofprint

Résumé

There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10 We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. Adoptive cell therapy with off-the-shelf CD45RA NCT04578210.

Sections du résumé

BACKGROUND AIMS OBJECTIVE
There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA
METHODS METHODS
Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10
RESULTS RESULTS
We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events.
CONCLUSIONS CONCLUSIONS
Adoptive cell therapy with off-the-shelf CD45RA
TRIAL REGISTRATION BACKGROUND
NCT04578210.

Identifiants

pubmed: 37897472
pii: S1465-3249(23)01056-3
doi: 10.1016/j.jcyt.2023.10.002
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT04578210']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest CF, AP-M and BS filed patent PCT/EP2021/076516 on Memory T cells as adoptive cell therapy for viral diseases. All other authors have no commercial, proprietary or financial interest in the products or companies described in this article.

Auteurs

Cristina Ferreras (C)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.

Clara Hernández-Blanco (C)

Internal Medicine Department, Hospital de Emergencias Enfermera Isabel Zendal, Madrid, Spain.

Alejandro Martín-Quirós (A)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Karima Al-Akioui-Sanz (K)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.

Marta Mora-Rillo (M)

Infectious Diseases Unit, Internal Medicine Department, University Hospital La Paz, Hospital La Paz Institute for Health Research, IdiPAZ, Consorcio Centro de Investigación Biomédica en Red CIBER-Infec, Madrid, Spain.

Fátima Ibáñez (F)

Internal Medicine Department, Hospital Puerta de Hierro, Madrid, Spain.

Mariana Díaz-Almirón (M)

Biostatistics Department, La Paz University Hospital, Madrid, Spain.

Jordi Cano-Ochando (J)

Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Madrid, Spain; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Daniel Lozano-Ojalvo (D)

Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

María Jiménez-González (M)

Infectious Diseases Unit, Internal Medicine Department, University Hospital La Paz, Hospital La Paz Institute for Health Research, IdiPAZ, Consorcio Centro de Investigación Biomédica en Red CIBER-Infec, Madrid, Spain; Clinical Trials Unit (UCICEC) at Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.

Rosa Goterris (R)

Hematology Department, Hospital Clinico Universitario, Valencia, Spain.

Elena Sánchez-Zapardiel (E)

Immunology Department, University Hospital La Paz, Madrid, Spain.

Raquel de Paz (R)

Hematology Department, University Hospital La Paz, Madrid, Spain.

Pilar Guerra-García (P)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain; Pediatric Hemato-Oncology Department, University Hospital La Paz, Madrid, Spain.

Javier Queiruga-Parada (J)

Clinical Pharmacology Department, University Hospital La Paz, Madrid, Spain.

Pablo Molina (P)

Clinical Pharmacology Department, University Hospital La Paz, Madrid, Spain.

María Luisa Briones (ML)

Neumology Department, Hospital Clinico Universitario, Valencia, Spain.

Beatriz Ruz-Caracuel (B)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.

Alberto M Borobia (AM)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain; Clinical Trials Unit (UCICEC) at Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain; Clinical Pharmacology Department, University Hospital La Paz, Madrid, Spain.

Antonio J Carcas (AJ)

Clinical Trials Unit (UCICEC) at Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain; Clinical Pharmacology Department, University Hospital La Paz, Madrid, Spain; Faculty of Medicine Universidad Autónoma de Madrid, Madrid, Spain.

Dolores Planelles (D)

Department of Histocompatibility, Centro de Transfusión de la Comunidad Valenciana, Valencia, Spain.

José Luis Vicario (JL)

Histocompatibility, Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain.

Miguel Ángel Moreno (MÁ)

Histocompatibility, Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain.

Antonio Balas (A)

Histocompatibility, Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain.

Marta Llano (M)

Infectious Diseases Department, Hospital de Emergencias Enfermera Isabel Zendal, Madrid, Spain.

Andrea Llorente (A)

Infectious Diseases Department, Hospital de Emergencias Enfermera Isabel Zendal, Madrid, Spain.

Álvaro Del Balzo (Á)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Carlos Cañada (C)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Miguel Ángel García (MÁ)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

María Elena Calvin (ME)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Isabel Arenas (I)

Emergency Unit, Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Rebeca Pérez de Diego (R)

Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Interdepartmental Group of Immunodeficiencies, Madrid, Spain.

Cristina Eguizábal (C)

Research Unit, Basque Centre for Blood Transfusion and Human Tissues, Osakidetza, Bizkaia, Spain; Biocruces Bizkaia Health Research Institute, Bizkaia, Spain.

Bernat Soria (B)

Health Research Institute-ISABIAL, Alicante University Hospital and Institute of Bioengineering, Miguel Hernández University, Alicante, Spain; University Pablo de Olavide, Sevilla, Spain.

Carlos Solano (C)

Hematology Department, Hospital Clinico Universitario, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain.

Antonio Pérez-Martínez (A)

Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain; Pediatric Hemato-Oncology Department, University Hospital La Paz, Madrid, Spain; Faculty of Medicine Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: aperezmartinez@salud.madrid.org.

Classifications MeSH