Off-the-shelf CD5CAR-NK Cells for Refractory Invasive Mold Disease: Phase I Clinical Trial.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Evaluate the safety of allogeneic CD5CAR-CBNK cells in patients with refractory mold infection.
研究概览
简要总结
CD5CAR-NK is a first-in-human, pilot, dose-escalation, and single-site study to evaluate the safety of CD5CAR-CBNK in patients with invasive mold diseases (IMD).
The study population consists of patients aged ≥18 years with refractory mold infections.
The number of patients treated will be 10. This is a dose-escalation study including 3 cohorts.
详细描述
CD5CAR-NK is a first-in-human, pilot, dose-escalation, and single-site study to evaluate the safety of CD5CAR-CBNK in patients with invasive mold diseases (IMD).
The study population consists of patients aged ≥18 years with refractory mold infections.
The number of patients treated will be 10.
This is a dose-escalation study including 3 cohorts. The dose escalation scheme will follow the following scheme:
Cohort 1(3 patients) The sentinel patient of cohort 1 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at day 0. Intra-patient safety will be reviewed daily following the first dose. The second dose (day+3) and third (day+6) will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Diagnosis of probable or proven fungal infection according to EORTC criteria20, who have been treated with the best available antifungal strategy and present at least one of the following criteria indicating inadequate response to antifungal therapy: Increase in fungal infection biomarker levels (serum or bronchoalveolar lavage galactomannan, or serum β-D-glucan) after at least one week of antifungal therapy:
- •Persistence of positive cultures despite having received ≥2 weeks of appropriate antifungal treatment.
- •Radiological worsening of lesions suggestive of fungal infection despite having received ≥2 weeks of appropriate antifungal treatment, and when at least 2 weeks have passed since the previous imaging study.
- •Clinical deterioration and microbiological isolation of a fungus resistant to all available antifungal treatments (including cases in which a specific antifungal cannot be administered due to the risk of unacceptable toxicity).
- •Rapidly progressive clinical deterioration despite the implementation of all available antifungal measures, conferring a poor prognosis for the patient.
- •Signing the informed consent form to participate in the clinical trial and to receive CD5CAR-CBNK therapy. If the patient is not in a condition to sign the informed consent form, consent will be requested from the family and patient consent for the study continuation will be obtained as soon as deemed possible.
排除标准
- •An expected survival of less than four weeks due to a cause unrelated to the current fungal infection.
- •Patients with positive HIV serology.
- •Pregnant or breastfeeding women.
- •Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study.
研究组 & 干预措施
Cohort 1
The sentinel patient of cohort 1 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at day 0. Intra-patient safety will be reviewed daily following the first dose. The second dose (day+3) and third (day+6) will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).
Cohort 1 is planned to include 3 evaluable patients. The first subject in each cohort will be dosed and undergo a safety observation period between administrations. The second subject will be dosed 7 days after the first subject completes treatment and after review of safety data. The third subject will be dosed 3 days after the last dose of the second subject, subject to confirmation of acceptable safety.
干预措施: CD5CAR-CBNK (Genetic)
Cohort 2
The sentinel patient of cohort 2 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12. Intra-patient safety will be reviewed daily following the first 25 million dose. The dose at day +12 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).
干预措施: CD5CAR-CBNK (Genetic)
Cohort 3
The sentinel patient of cohort 3 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12, and additionally 50 x106 CAR+ cells at days 15 and 18. In this occasion, intra-patient safety will be reviewed daily following the first 50 million dose. The dose at day +18 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).
干预措施: CD5CAR-CBNK (Genetic)
结局指标
主要结局
Evaluate the safety of allogeneic CD5CAR-CBNK cells in patients with refractory mold infection.
时间窗: 28 days following the first infusion
Number and proportion of patients with grade 3-4 treatment-related adverse events according to the Common Toxicity Criteria (CTCAE) version 5.0
次要结局
- Evaluate the safety and tolerability of CD5CAR-CBNK cells.(at 6 and 12 weeks)
- Evaluate the safety and tolerability of CD5CAR-CBNK cells.(During the first year after first administration)
- Assess the efficacy of CD5CAR-CBNK cells.(at day 15, day 28, 6 and 12 weeks.)
- Assess the efficacy of CD5CAR-CBNK cells.(at day 28, 6 and 12 weeks from the first CD5CAR-CBNK cell infusion and from study inclusion.)
- Assess the efficacy of CD5CAR-CBNK cells.(at day 28, 6 and 12 weeks from the CD5CAR-CBNK cell infusion and inclusion of the patient.)
- Assess the efficacy of CD5CAR-CBNK cells.(During the first year after first administration)
- To quantify persistence and kinetics of allogeneic CD5CAR-CBNK cells in blood after administration.(During the first year after first administration)