Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
研究概览
简要总结
Radiation therapy is one of the main means for treating malignant tumor, during which radioactive lung injury is inevitable. Currently there is nearly no effective clinical treatment for late post-radiotherapy pulmonary fibrosis. This study intends to carry out an open, single-center, non-randomized phase I clinical trial. During the treatment, the local lesions will be fully lavaged, and then clinical grade umbilical cord mesenchymal stem cells (MSCs) will be injected directly into the lesion by fiberoptic bronchoscopy. After six-month observation, the investigators will initially evaluate the safety and effectiveness of the treatment by measuring two key indicators-the CT density histogram and the patients' self-evaluation, and one secondary indicator-the changes of TGF-β1 contents, both before and after the treatment. Meanwhile, the investigators will make a preliminary discuss about the possible immunomodulatory effects of the umbilical cord MSCs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-70 years old.
- •Subjects with a clear history of malignancy.
- •Subjects with a clear history of chest radiation therapy at least 3 months earlier.
- •Subjects diagnosed as chronic phase of radiation-induced pneumonitis or radiation-induced pulmonary fibrosis stage (see Annex 3 for diagnosis).
- •Subjects signed informed consent.
排除标准
- •Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures.
- •Subjects with syphilis or HIV positive antibody.
- •Subjects with infection aggravated within the past month.
- •Subjects suffering from any of the following pulmonary diseases: active tuberculosis, pulmonary embolism, pneumothorax, multiple huge bullae, uncontrolled asthma, severe pneumonia, acute exacerbation of chronic bronchitis, AECOPD, severe and / or extremely severe COPD, etc..
- •Subjects suffering from other serious diseases, such as myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis.
- •Subjects with progression-free survival (PFS) less than 0.5 years or Karnofsky performance scores less than 60 points.
- •Subjects with leukopenia (WBC less than 4x109 / L) or agranulocytosis (WBC less than 1.5x109 / L or neutrophils less than 0.5x109 / L) caused by any reason.
- •Subjects with severe renal impairment, serum creatinine> 1.5 times the upper limit of normal.
- •Subjects with liver disease or liver damage: ALT, AST, total bilirubin> 2 times the upper limit of normal
- •Subjects with a history of mental illness or suicide risk, with a history of epilepsy or other central nervous system disorders.
- •Subjects with severe arrhythmias (such as ventricular tachycardia, frequent superventricular tachycardia, atrial fibrillation, and atrial flutter, etc.) or cardiac degree II or above conduction abnormalities displayed via 12-lead ECG.
- •Subjects with a history of alcohol or illicit drug abuse.
- •Subjects accepted by any other clinical trials within 3 months before the enrollment
- •Subjects with poor compliance, difficult to complete the study.
- •Any other conditions that might increase the risk of subjects or interfere with the clinical trial.
研究组 & 干预措施
treatment group
Patients will receive 10^6 (1 million) /Kg/person cells of clinical grade umbilical cord mesenchymal stem cells (MSCs) injected via fiberoptic bronchoscopy after fully lavage of the localized lesions
干预措施: clinical grade umbilical cord mesenchymal stem cells (Biological)
结局指标
主要结局
Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
时间窗: 6 months
Different proportions will be assigned to the three indicators. The overall curative effect can be judged with scores ranging from 0 to100. Specific proportions are as follows: full scores of 50 points for image changes, 25 for self-efficacy evaluation and 25 for TGF-β1 content changes. The image changes can be classified into four levels: significant control, improved, stable, and progressive; the self-efficacy evaluation can also be classified into four levels: effective, improved, stable and invalid; the changes of TGF-β1 content will be classified into three levels: improved, stable, and progressive. The four levels will be scored on the ratio of 5:4:3:1, the three levels will be scored on the ratio of 5:3:1.
Safety Evaluation
时间窗: 6 months
Clinical adverse events evaluated as definitely/ probably/possibly concerned with stem cell therapy in this trial and abnormal results of laboratory tests or other special examinations will be observed and recorded in detail.
次要结局
- Clinical Indicator 2: change in pulmonary function analysis(3-6 months)
- Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)(6 months)
- Clinical Indicator 3: 6-minute walk test distance(3-6 months)
- Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)(3-6 months)
- Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage(6 months)
- Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)(3-6 months)
- Clinical Indicator 4: change in MRC chronic dyspnea scale(3-6 months)
- Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale(3-6 months)
- Immunological Indicator in serum 6: expression levels of IL-12, IL-10(3-6 months)
- Clinical Indicator 1: change in blood gas analysis(3-6 months)
- Immunological Indicator in serum 3: concent of immunoglobulin(3-6 months)
- Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage(3-6 months)
- Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)(6 months)
- Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)(6 months)
- Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)(3 months)
- Fibrosis Indicators in serum 2: content of hydroxyproline(3-6 months)
- Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)(3-6 months)
- Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood(6 months)
- Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10(6 months)
- Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)(3-6 months)
- Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood(3-6 months)
- Immunological Indicator in lavage fluid 3: concent of immunoglobulin(6 months)
- Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)(6 months)
- Fibrosis Indicators in lavage fluid 2: content of hydroxyproline(6 months)
研究者
Jianwu Dai
Principal Investigator of Regenerative Medicine Laboratory, Institute of Genetics and Developmental Biology, CAS
Chinese Academy of Sciences