Back to resultsA Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Primary Purpose
Post-radiotherapy Pulmonary Fibrosis
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
clinical grade umbilical cord mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Post-radiotherapy Pulmonary Fibrosis focused on measuring radiation-induced pulmonary fibrosis, MSCs
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
treatment group
Arm Description
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
Outcomes
Primary Outcome Measures
Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
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
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.
Secondary Outcome Measures
Clinical Indicator 1: change in blood gas analysis
Clinical Indicator 2: change in pulmonary function analysis
Clinical Indicator 3: 6-minute walk test distance
Clinical Indicator 4: change in MRC chronic dyspnea scale
Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale
Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in serum
Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in serum
Immunological Indicator in serum 3: concent of immunoglobulin
Humoral immunological indicator: concent of immunoglobulin measured in serum
Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
Humoral immunological indicator: expression levels of various cytokines in serum (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in serum
Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in serum
Immunological Indicator in serum 6: expression levels of IL-12, IL-10
Macrophage- related polarization indicators: expression levels of IL-12, IL-10 measured in serum
Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in lavage fluid
Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in lavage fluid
Immunological Indicator in lavage fluid 3: concent of immunoglobulin
Humoral immunological indicator: concent of immunoglobulin measured in lavage fluid
Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
Humoral immunological indicator: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in lavage fluid
Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in lavage fluid
Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10
Macrophage-related polarization indicators: expression levels of IL-12, IL-10 measured in lavage fluid
Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)
Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Content of transforming growth factor α/β (TGF-α/TGF-β) measured in serum
Fibrosis Indicators in serum 2: content of hydroxyproline
Content of hydroxyproline measured in serum
Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in serum
Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Content of transforming growth factor -α/β (TGF-α/TGF-β) measured in lavage fluid
Fibrosis Indicators in lavage fluid 2: content of hydroxyproline
Content of hydroxyproline measured in lavage fluid measured in lavage fluid
Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in lavage fluid
Full Information
NCT ID
NCT02277145
First Posted
October 20, 2014
Last Updated
July 23, 2019
Sponsor
Jianwu Dai
Collaborators
Southwest Hospital, China
1. Study Identification
Unique Protocol Identification Number
NCT02277145
Brief Title
A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Official Title
Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jianwu Dai
Collaborators
Southwest Hospital, China
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-radiotherapy Pulmonary Fibrosis
Keywords
radiation-induced pulmonary fibrosis, MSCs
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
treatment group
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
clinical grade umbilical cord mesenchymal stem cells
Intervention Description
10^6 (1 million) /Kg/person cells of clinical grade umbilical cord MSCs will be injected after fully lavage of the localized lesions
Primary Outcome Measure Information:
Title
Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
Description
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.
Time Frame
6 months
Title
Safety Evaluation
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Clinical Indicator 1: change in blood gas analysis
Time Frame
3-6 months
Title
Clinical Indicator 2: change in pulmonary function analysis
Time Frame
3-6 months
Title
Clinical Indicator 3: 6-minute walk test distance
Time Frame
3-6 months
Title
Clinical Indicator 4: change in MRC chronic dyspnea scale
Time Frame
3-6 months
Title
Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale
Time Frame
3-6 months
Title
Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood
Description
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Description
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in serum 3: concent of immunoglobulin
Description
Humoral immunological indicator: concent of immunoglobulin measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
Description
Humoral immunological indicator: expression levels of various cytokines in serum (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage
Description
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in serum 6: expression levels of IL-12, IL-10
Description
Macrophage- related polarization indicators: expression levels of IL-12, IL-10 measured in serum
Time Frame
3-6 months
Title
Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood
Description
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in lavage fluid
Time Frame
6 months
Title
Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Description
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in lavage fluid
Time Frame
6 months
Title
Immunological Indicator in lavage fluid 3: concent of immunoglobulin
Description
Humoral immunological indicator: concent of immunoglobulin measured in lavage fluid
Time Frame
6 months
Title
Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
Description
Humoral immunological indicator: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in lavage fluid
Time Frame
6 months
Title
Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage
Description
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in lavage fluid
Time Frame
6 months
Title
Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10
Description
Macrophage-related polarization indicators: expression levels of IL-12, IL-10 measured in lavage fluid
Time Frame
6 months
Title
Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)
Time Frame
3 months
Title
Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Description
Content of transforming growth factor α/β (TGF-α/TGF-β) measured in serum
Time Frame
3-6 months
Title
Fibrosis Indicators in serum 2: content of hydroxyproline
Description
Content of hydroxyproline measured in serum
Time Frame
3-6 months
Title
Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Description
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in serum
Time Frame
3-6 months
Title
Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Description
Content of transforming growth factor -α/β (TGF-α/TGF-β) measured in lavage fluid
Time Frame
6 months
Title
Fibrosis Indicators in lavage fluid 2: content of hydroxyproline
Description
Content of hydroxyproline measured in lavage fluid measured in lavage fluid
Time Frame
6 months
Title
Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Description
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in lavage fluid
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JianWu Dai, Ph.D
Organizational Affiliation
Chinese Academy of Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wei Xiong, M.D
Organizational Affiliation
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Xiaotian Dai, M.M
Organizational Affiliation
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Official's Role
Study Director
Facility Information:
Facility Name
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400038
Country
China
12. IPD Sharing Statement
Learn more about this trial
A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
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