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
© 2021. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Trials - 22(2021), 1 vom: 02. Okt., Seite 674 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
García-García, I [VerfasserIn] |
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| Links: |
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| Themen: |
Allogeneic |
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| Anmerkungen: |
Date Completed 05.10.2021 Date Revised 03.04.2024 published: Electronic ClinicalTrials.gov: NCT04578210 Citation Status MEDLINE |
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| doi: |
10.1186/s13063-021-05625-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a García-García, I |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |b RELEASE study protocol |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 05.10.2021 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04578210 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020 | ||
| 650 | 4 | |a Clinical Trial Protocol | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Allogeneic | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Lymphopenia | |
| 650 | 4 | |a Memory T cells | |
| 650 | 4 | |a NK cells | |
| 650 | 4 | |a Pneumonia | |
| 650 | 4 | |a Protocol | |
| 650 | 4 | |a Safety | |
| 700 | 1 | |a Guerra-García, P |e verfasserin |4 aut | |
| 700 | 1 | |a Ferreras, C |e verfasserin |4 aut | |
| 700 | 1 | |a Borobia, A M |e verfasserin |4 aut | |
| 700 | 1 | |a Carcas, A J |e verfasserin |4 aut | |
| 700 | 1 | |a Queiruga-Parada, J |e verfasserin |4 aut | |
| 700 | 1 | |a Vicario, J L |e verfasserin |4 aut | |
| 700 | 1 | |a Mirones, I |e verfasserin |4 aut | |
| 700 | 1 | |a Solano, C |e verfasserin |4 aut | |
| 700 | 1 | |a Eguizabal, C |e verfasserin |4 aut | |
| 700 | 1 | |a Soria, B |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Martínez, A |e verfasserin |4 aut | |
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