Dead Mesenchymal Stem Cells for Radiation Lung Injury

Study Overview
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Brief Summary
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The aim of this single center, single arm and prospective study is to explore the safety and efficacy of hDMSCs in the treatment of radiation pneumonitis.

Detailed Description
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As a single-center, single-arm, prospective clinical trial, this study aims to explore the safety and efficacy of hDMSCs in the treatment of radiation pneumonia. This study will include patients who have received chest radiation therapy and are diagnosed with radiation lung injury based on clinical manifestations and changes in chest CT imaging. The degree of lung injury is graded according to CTCAE v5.0 criteria, and the corresponding standard treatment is received according to its grade. Using the 3+3 design for dose climbing, according to the order of patient inclusion, the first 3 patients (cohort 1) are treated with a standard treatment regimen combined with a pre-specified starting dose of dead mesenchymal stem cells (this study does not set up a live MSC group as a control). There are currently no relevant research results of previous human trials. The starting dose is obtained by our preclinical research. The mouse dose is 1×10^5/pc/30g, that is, the effective dose of mice is 3.3×10^6/kg. The dose of mice is 10 times that of humans, and the effective dose of humans is 3.3×10^5/kg. Therefore, the clinical effective dose of 60kg patients is 2.0×10^7, infusion every 3 days, continuous infusion 4 times, treatment duration of 4 6 weeks. During the dose-limited toxicity (DLT) observation period (30 days), observe the number of cases of DLT in 3 patients to determine whether to maintain the current dose group or adjust the dose group. If the dose of dead mesenchymal stem cells needs to be increased, the dose is ramped up by 3 times the starting dose (i.e., the second gradient dose is 6.0×10^7) until the number of patients in either dose group reaches 6 or the dose group adjustment is not possible. To determine the optimal therapeutic dose for the treatment of radiation lung injury using death mesenchymal stem cells in combination with standard therapy. A total of 15 patients were planned to be included in this study.

Official Title
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Dead Mesenchymal Stem Cells for the Treatment of Radiation Lung Injury

Conditions
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Radiation Lung Injury

Intervention / Treatment
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* Biological: Death mesenchymal stem cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received chest radiotherapy; EOCG PS score of 0 to 3 points; Diagnosis of radiation lung injury by the attending physician, grade 2 to 3 (according to the CTCAE v5.0 standards); Main organs function is normal, that meet the following criteria: blood routine examination (within 7 days of unused hematopoietic growth factors and blood transfusion) : ANC ≥ 1.5 x 10^9 / L, PLT ≥ 80 x 10^9 / L, HGB ≥ 80 g/L;Biochemical examination: TBil ≤ 1.5 x ULN (upper limit of normal);ALT or AST ≤ 2.5 x ULN; Creatinine clearance ≥ 60 mL/min (Cockcroft - Gault formula); Blood coagulation function: INR or PT ≤ 1.5 x ULN, if the subjects are receiving anticoagulant therapy, as long as the scope of PT in anticoagulant drugs for it. Heart function examination, electrocardiogram (ECG) normal or abnormal ECG (by the researchers to determine the clinical significance). Heart doppler ultrasound assessment: LVEF ≥ 50%; Radiation lung injury lasts less than 2 months； Survival expectation ≥6 months; Signed and dated written informed consent Exclusion Criteria: Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures; People with a history of chronic bronchitis, emphysema, or cor pulmonale; History of lung resection surgery; Tumor progression; People with severe lung infection; Uncontrollable severe systemic diseases (e.g., central nervous system, cardiovascular system, blood system, digestive system, endocrine system, respiratory system, genitourinary system, immune system, etc.) and psychosis; Serious cardiovascular events: a period of 6 months in heart failure (NYHA class III level IV), myocardial infarction, unstable angina, severe arrhythmia, cerebral infarction, cerebral hemorrhage; Abnormal liver and kidney function: AST and ALT exceed the upper limit of normal by 2.5 times. Serum creatinine is greater than 1.5 mg/dl in men and 1.4 mg/dl in women; Co-infection with HIV, Treponema pallidum, tuberculosis, influenza virus, adenovirus and other respiratory infections; Hemorrhage or thrombosis, bleeding or anticoagulant drugs; Combined with cachexia or other organ failure (requiring organ support); Shock or invasive ventilation; Combined with pulmonary interstitial pneumonia caused by other reasons or damage, or lung imaging showed radioactive lung injury diagnosed with pulmonary interstitial pneumonia or damage before; Patients who have participated in clinical studies of stem cells; The investigators believed that there were other reasons why participants were not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: one-arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia<br>Subjects (n=3) received a standard treatment regimen combined with a pre-specified starting dose of dead mesenchymal stem cells (2.0×10^7 for 60kg patient), infusion every 3 days, continuous infusion 4 times, treatment duration is 4 6 weeks. . If dose-limiting toxicity (DLT) does not occur within 30 days of the first administration, the dose is escalated by three times. | Biological: Death mesenchymal stem cell<br>* A standard treatment regimen combined with a pre-specified starting dose of dead mesenchymal stem cells (2.0×10^7 for 60kg patient), infusion every 3 days, continuous infusion 4 times, treatment duration is 4 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of adverse events | The number of adverse events occurring within a given time frame will be reported according to CTCAE v5.0 to assess overall safety. | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest contrast-enhanced CT will be used to assess changes in lung injury after treatment | Chest contrast-enhanced CT will be performed at 1, 2, 3, 6, and 12 months after completion of dead mesenchymal stem cell injection, and the change in the proportion of total lesions to total lung volume will be calculated, i.e., (proportion of total lesions to total lung volume - proportion of total lesions to total lung volume at baseline) / proportion of total lesions to total lung volume at baseline. | up to 1 year | 
| Blood gas analysis will be performed after 1 month of dead mesenchymal stem cell injection. | At 1 month after completion of the injection of dead mesenchymal stem cells, changes in blood gas analysis will be observed to assess lung function. | up to 1 year | 
| Pulmonary function test will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection. | At after 1, 2, 3, 6, 12month completion of the injection of dead mesenchymal stem cells, pulmonary function test will be performed to assess recovery of lung function. | up to 1 year | 
| 6-minute walking tests will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection. | At 1, 2, 3, 6 and 12 months after the completion of dead mesenchymal stem cell therapy, 6-minute walking tests will be performed to evaluate the recovery of the subjects' cardiopulmonary condition. | up to 1 year | 
| St. George's Respiratory Questionnaire will be completed to estimate the quality of life after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection. | At 1, 2, 3, 6 and 12 months after the completion of dead mesenchymal stem cell therapy, St. George's Respiratory Questionnaire will be completed to evaluate the subjects' quality of life. | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dead Mesenchymal Stem Cells, Radiation Lung Injury, Treatment