Exploration of the Predictive Marker and Establishment of Predictive Models of Checkpoint Inhibitor Pneumonitis

Exploration of Predictive Markers and Establishment of Predictive Models for Checkpoint Inhibitor Pneumonitis in Combination With Imaging in Immune Checkpoint Inhibitor Therapy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumonia, Interstitial
• Intervention / Treatment: Other: Immune checkpoint inhibitors(ICIs) therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 440

Contacts and Locations

• Study Contact: Name: Hui Guo, PH.D; Phone Number: 0086-13572824106; Email: guohuihappy97@163.com
• Study Contact Backup: Name: Xiaohui Jia; Phone Number: 0086-19829393046; Email: xiaohuijia0101@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with malignant tumor receiving immune checkpoint inhibitors for the first time.

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
observational group; Patients receiving ICIs for the first time	Other: Immune checkpoint inhibitors(ICIs) therapy; Patients with malignant tumors who first received ICIs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of C reactive protein(CRP); mg/L	CRP level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Interleukin-6(IL-6); Pg/ml	IL-6 level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
CD4+ T lymphocyte; /uL	The absolute and relative counts of CD4+ T lymphocyte in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
CD4+ T lymphocyte; percent	Percentage of CD4+ T lymphocyte in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
CD8+ T lymphocyte; /uL	The absolute and relative counts of CD8+ T lymphocyte in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
CD8+ T lymphocyte; percent	Percentage of CD8+ T lymphocyte in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
NK cell; /uL	The absolute and relative counts of NK cell in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
NK cell; percent	Percentage of NK cell in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
White blood cell count; 10^9/L	The white blood cell count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Lymphocyte count; 10^9/L	The absolute and relative counts of total lymphocyte count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Lymphocyte count; percent	Percentage of total lymphocyte count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Eosinophils count; 10^9/L	The absolute and relative counts of eosinophils count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Eosinophils count; percent	Percentage of eosinophils count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Blood platelet count; 10^9/L	The blood platelet count in whole blood.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Alanine aminotransferase(ALT); U/L	The ALT level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Aspartate aminotransferase (AST); U/L	The AST level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Serum albumin; g/L	The albumin level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
γ-glutamyl transpeptadase（γ-GGT); U/L	The γ-GGT level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Smoking index	The average root number per day multiplied by smoking years of smoking, that is, smoking index.	At baseline
Body mass index (BMI); kg/m^2	The body's weight(Kg) divided by the square of your height(m), that is, body mass index.	At baseline
Serum procalcitonin(PCT); ng/ml	The PCT level in the serum.	Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
Forced vital capacity(FVC); L	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.	Before Cycle 1.
Forced the first second of expiratory volume (FEV1); L	the first second of exhalation during the maximum exhalation after the maximum deep inhalation. FEV1 was used to evaluate pulmonary ventilation function.	Before Cycle 1.
FEV1/FVC; percent	FEV1 accounts for the percentage of FVC. FEV1/FVC was used to evaluate pulmonary ventilation function.	Before Cycle 1.
Maximal mid-expiratory flow(MMEF); L/s	The average flow rate with forced exhalation of 25% to 75% of lung capacity. FEV1/FVC was used to evaluate pulmonary ventilation function.	Before Cycle 1.
Fractional exhaled nitric oxide (FeNO) measurement；ppb	FeNO measurement quantified the amount of nitric oxide (NO) in one's exhaled breath, which was used to evaluate pulmonary diffusion function.	Before Cycle 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of IRP; percent	The incidence of IRP in the general population receiving ICIs	Up to 36 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Fujian Cancer Hospital; Henan Cancer Hospital; The First Affiliated Hospital of Zhengzhou University; Wuhan Union Hospital, China; Tang-Du Hospital
• Investigators: Principal Investigator: Hui Guo, PH.D, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Anticipated): August 20, 2021
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; predictive model; immune checkpoint inhibitors; predictive marker
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Lung Diseases, Interstitial; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: XJTU1AF2021LSK-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No