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
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, tolerabil...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-021-05625-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | I. García-García |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-17T12:41:51Z |
| format | Article |
| id | doaj.art-27dbb45a41e14236a7f191a27f3d24f1 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-17T12:41:51Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-27dbb45a41e14236a7f191a27f3d24f12022-12-21T21:47:56ZengBMCTrials1745-62152021-10-0122111210.1186/s13063-021-05625-7A 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 protocolI. García-García0P. Guerra-García1C. Ferreras2A. M. Borobia3A. J. Carcas4J. Queiruga-Parada5J. L. Vicario6I. Mirones7C. Solano8C. Eguizabal9B. Soria10A. Pérez-Martínez11Clinical Pharmacology Department, University Hospital La PazClinical Pharmacology Department, University Hospital La PazHospital La Paz Institute for Health Research, IdiPAZ, University Hospital La PazClinical Pharmacology Department, University Hospital La PazClinical Pharmacology Department, University Hospital La PazClinical Pharmacology Department, University Hospital La PazRegional Blood Transfusion CentrePediatric Hemato-oncology Department, University Hospital La PazHospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Universidad de ValenciaResearch Unit, Basque Center for Blood Transfusion and Human Tissues, OsakidetzaInstitute of Bioengineering, Miguel Hernández UniversityPediatric Hemato-oncology Department, University Hospital La PazAbstract 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, 2020https://doi.org/10.1186/s13063-021-05625-7COVID-19ProtocolAllogeneicMemory T cellsNK cellsLymphopenia |
| spellingShingle | 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 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 Trials COVID-19 Protocol Allogeneic Memory T cells NK cells Lymphopenia |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | COVID-19 Protocol Allogeneic Memory T cells NK cells Lymphopenia |
| url | https://doi.org/10.1186/s13063-021-05625-7 |
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