Clinical Pharmacology Department, University Hospital La Paz, Madrid, Spain.
Pediatric Hemato-oncology Department, University Hospital La Paz, Madrid, Spain.
Trials. 2021 Oct 2;22(1):674. doi: 10.1186/s13063-021-05625-7.
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.
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.
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.
ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020.
COVID-19 的中重度病例表现出免疫系统失调，T 细胞淋巴细胞减少和炎症过度活跃。这是一项开放标签、多中心、双臂、随机、剂量递增的 I/II 期临床试验方案，旨在评估同种异体记忆 T 细胞和自然杀伤 (NK) 细胞在淋巴细胞减少和/或肺炎的 COVID-19 患者中的给药安全性、耐受性、同种反应性和疗效。本研究的目的是确定该治疗中度/重度 COVID-19 患者的推荐 2 期剂量 (RP2D) 的安全性和疗效。
在 I 期试验中，将 18 例 COVID-19 相关肺炎和/或淋巴细胞减少症患者（无缺氧需求或仅需通过鼻导管吸氧 2.5 升/分钟以下），根据供体和患者的生物学特性，分为两组。A 组治疗包括给予递增剂量的记忆 T 细胞和标准治疗（SoC）。B 组治疗包括给予递增剂量的 NK 细胞和 SoC。在 II 期试验中，总共 182 例 COVID-19 相关肺炎和/或淋巴细胞减少症患者需要或不需要补充氧气，但无需机械通气，将根据 HLA 分型分配到 A 组或 B 组。在每个臂内，他们将以 1:1 的比例随机分组。在 A 组中，患者将接受 SoC 或记忆 T 细胞的 RP2D 加 SoC。在 B 组中，患者将接受 SoC 或 NK 细胞的 RP2D 加 SoC。
我们假设从 COVID-19 中康复的恢复期供体获得的 SARS-CoV-2 特异性记忆 T 淋巴细胞可用作被动细胞免疫疗法，以治疗中度/重度患者的肺炎和淋巴细胞减少症。COVID-19 引起的淋巴细胞减少症构成了一个治疗窗口，可能有助于供体植入和病毒保护，直至康复。
ClinicalTrials.gov NCT04578210。首次发布：2020 年 10 月 8 日。
