Exploration of Predictive Markers and Establishment of Predictive Models for Checkpoint Inhibitor Pneumonitis in Combination With Imaging in Immune Checkpoint Inhibitor Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 440
- 主要终点
- CD4+ T lymphocyte; percent
研究概览
简要总结
This is a prospective, multicenter observational study to explore the predictive factors of checkpoint inhibitor pneumonitis (CIP) and to establish predictive models by combining imaging information for IRP. The imaging type of CIP, the pathological type, various inflammatory cytokines and tumor proportion score(TPS) of PD-L1 expression level, etc. will be paid more attention.
详细描述
Prospective dual-arm, multicenter observational study to explore the predictive factors of checkpoint inhibitor pneumonitis (CIP) and to establish predictive models by combining imaging information.Patients will receive work-up, treatment and follow-up exclusively as routinely done except monitoring and evaluation of CIP. Necessary tests will be required, such as lung function tests, lymphocyte subsets, and thin-section CT of the chest during evaluation of the disease.This study mainly included patients with malignant tumor who received immune checkpoint inhibitors for the first time.Fasting venous blood was taken before treatment and before cycle 3,5...2n+1 of treatment. Then the blood samples were centrifuged and frozen in a refrigerator at -80℃ for later mass spectrometry analysis. IrAEs of patients was strictly recorded according to CommonTerminology Criteria Adverse Events V4.0 (CTCAE V4.0). The main objective was to explore the relationship between various indicators and the occurrence of CIP, including pulmonary ventilation and diffusion function at baseline, C-reative protein(CRP), cytokines, interleukin-6(IL-6), CD4+ T lymphocyte count and percentage, CD8+ T lymphocyte count and percentage, NK cell count and percentage, total T lymphocyte count and percentage, neutrophil counts and percentages, eosinophilic cell count and percentage, white blood cell count, blood platelet count, serum albumin(ALB), alanine aminotransferase(ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase（γ-GGT), body mass index (BMI), serum procalcitonin(PCT), smoking index and various inflammatory cytokines.
Primary study endpoints: The predictive factors and the predictive models of CIP.
Secondary study endpoints: The incidence and clinical characteristics of CIP.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age ≥ 18 years;
- •Obtain written informed consent and any locally required authorization from the patient or his/her legal representative prior to the commencement of any study protocol related procedures, including screening assessments;
- •Patients with malignant tumors confirmed by histology or cytology can be treated with ICIs after evaluation by a professional oncologist, with no restriction on cancer type or stage;
- •Life expectancy on day 1 ≥12 weeks;
- •When selected, the Eastern Cooperative Oncology Group (ECOG) physical status score was 0-2;
- •No previous use of immunotherapy；
- •No prior exposure to immune-mediated therapy;
- •Have sufficient viscera function and bone marrow function;
- •Evidence of postmenopausal status in women, or negative urine or serum pregnancy tests in premenopausal women.
排除标准
- •The target lesion had received immune-related treatment or immune-mediated treatment before;
- •Patients with clinically confirmed moderate to severe pulmonary interstitial fibrosis before taking ICIs;
- •Major surgical procedures were performed within 28 days of the first medication;
- •History of allograft transplantation;
- •Active or previously documented autoimmune or inflammatory diseases or other contraindications for immunotherapy;
- •Uncontrolled serious complications such as infection and acute cardio-cerebrovascular disease;
- •The presence of another primary malignancy;
- •anaphylaxis or hypersensitivity to immunotherapy or chemotherapy;
- •Decompensation of viscera and low bone marrow function and hematopoietic function；
- •Pregnant or lactating female patients;
- •Expected survival time < 3 months
结局指标
主要结局
CD4+ T lymphocyte; percent
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Percentage of CD4+ T lymphocyte in whole blood.
NK cell; /uL
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The absolute and relative counts of NK cell in whole blood.
NK cell; percent
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Percentage of NK cell in whole blood.
Eosinophils count; percent
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Percentage of eosinophils count in whole blood.
Serum albumin; g/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The albumin level in the serum.
Forced vital capacity(FVC); L
时间窗: Before Cycle 1.
The maximum amount of air that can be exhaled as soon as possible after the maximum inhalation. FVC was used to evaluate pulmonary ventilation function.
FEV1/FVC; percent
时间窗: Before Cycle 1.
FEV1 accounts for the percentage of FVC. FEV1/FVC was used to evaluate pulmonary ventilation function.
CD4+ T lymphocyte; /uL
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The absolute and relative counts of CD4+ T lymphocyte in whole blood.
CD8+ T lymphocyte; percent
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Percentage of CD8+ T lymphocyte in whole blood.
Eosinophils count; 10^9/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The absolute and relative counts of eosinophils count in whole blood.
Aspartate aminotransferase (AST); U/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The AST level in the serum.
The change of C reactive protein(CRP); mg/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
CRP level in the serum.
CD8+ T lymphocyte; /uL
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The absolute and relative counts of CD8+ T lymphocyte in whole blood.
Blood platelet count; 10^9/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The blood platelet count in whole blood.
Body mass index (BMI); kg/m^2
时间窗: At baseline
The body's weight(Kg) divided by the square of your height(m), that is, body mass index.
Lymphocyte count; 10^9/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The absolute and relative counts of total lymphocyte count in whole blood.
Fractional exhaled nitric oxide (FeNO) measurement；ppb
时间窗: Before Cycle 1.
FeNO measurement quantified the amount of nitric oxide (NO) in one's exhaled breath, which was used to evaluate pulmonary diffusion function.
Interleukin-6(IL-6); Pg/ml
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
IL-6 level in the serum.
White blood cell count; 10^9/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The white blood cell count in whole blood.
Lymphocyte count; percent
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Percentage of total lymphocyte count in whole blood.
Alanine aminotransferase(ALT); U/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The ALT level in the serum.
γ-glutamyl transpeptadase（γ-GGT); U/L
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The γ-GGT level in the serum.
Smoking index
时间窗: At baseline
The average root number per day multiplied by smoking years of smoking, that is, smoking index.
Maximal mid-expiratory flow(MMEF); L/s
时间窗: Before Cycle 1.
The average flow rate with forced exhalation of 25% to 75% of lung capacity. FEV1/FVC was used to evaluate pulmonary ventilation function.
Serum procalcitonin(PCT); ng/ml
时间窗: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
The PCT level in the serum.
Forced the first second of expiratory volume (FEV1); L
时间窗: Before Cycle 1.
the first second of exhalation during the maximum exhalation after the maximum deep inhalation. FEV1 was used to evaluate pulmonary ventilation function.
次要结局
- The incidence of IRP; percent(Up to 36 months)