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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Phase II
研究概览
简要总结
This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19.
Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state.
This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.
详细描述
In this phase I/II trial natural killer (NK) cells or memory T lymphocytes will be infused from donors who have recovered from COVID-19 and have complete resolution of symptoms for at least 14 days.
There will be two arms based on the biology of the donor and the patient:
Arm 1. Infusion of memory T cells from HLA partially match donors which have the SARS-COV-2 memory T cell repertoire.
Arm 2. Infusion of NK cells which are cells of the innate immune system that can eliminate virally infected cells.
The investigators expect a quick recovery of the patients with pneumonia or lymphopenia for two reasons:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- — 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients ≤ 80 years of age.
- •Patient with diagnosis of COVID-19 infection with laboratory confirmation by reverse-transcription PCR (RT-PCR) of SARS-CoV-2 <72 hours prior to study entry.
- •Onset of symptoms < 10 days prior to administration of study treatment.
- •No more than 72 hours (3 days) of hospitalization before study treatment administration.
- •Phase I criteria: Patients requiring hospitalization for COVID-19, with pneumonia diagnosed with chest radiograph or computed tomography imaging or lymphopenia (absolute lymphocyte counts below 1.2 x 109cells /L) AND O2Sat ≤ 94% on room air at screening, no oxygen requirement or with an oxygen need of ≤ 2.5 lpm in nasal cannula.
- •Phase II criteria: Patients requiring hospitalization with pneumonia diagnosed with chest radiograph or computed tomography imaging or lymphopenia (absolute lymphocyte counts below 1.2 x 109cells /L) AND O2Sat ≤ 94% on room air at screening, requiring or not oxygen supplementation (nasal cannula, oxygen mask with reservoir, non-invasive ventilation, etc), but excluding mechanical ventilation.
- •Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
- •Be willing and able to comply with study procedures.
- •Patients with the ability to comprehend and sign the informed consent
- •Written informed consent obtained prior to any screening procedures.
排除标准
- •Enrolled in another Clinical Trial for COVID
- •Rapidly progressive disease with anticipated life-expectancy <72 hours.
- •Patients requiring mechanical ventilation.
- •Patients with multiorgan failure.
- •Mild-moderate (grade ≥ 3) organ impairment (liver, kidney, respiratory), according to criteria from the National Cancer Institute (NCI CTCAE version 5.0).
- •Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
- •Have a known history of human immunodeficiency virus infection, Hepatitis B or Hepatitis C; testing is not required in the absence of prior documentation or known history.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- •Any other condition that, in the opinion if the Investigator, may interfere with the efficacy and/or safety evaluation of the trial.
研究组 & 干预措施
Arm A: allogeneic T memory cells
patients will receive memory T cells
干预措施: T memory cells and NK cells (Biological)
Arm B: allogeneic NK cells
patients will receive NK cells
干预措施: T memory cells and NK cells (Biological)
结局指标
主要结局
Phase II
时间窗: 3 months
Phase II primary outcome is the incidence of patient recovery infusing adoptive NK cells or adoptive memory T cells. Recovery is defined as the proportion of participants in each group with normalization of fever and oxygen saturation (criteria for normalization: temperature \< 38°C armpit, and SpO2 \> 94%, sustained for at least 24 h) or lymphopenia recovery through day 14.
Phase I: Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD
时间窗: 3 months
Any grade 3 or higher toxicity with an attribution of definitely or probably related to the infusion of the cells and any lower grade toxicity that increases to a grade 3 or higher as a direct result of the cell infusion.
次要结局
- Secondary Outcomes(3 months)