xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06021067</url>
    </required_header>
    <id_info>
      <org_study_id>RLI2023</org_study_id>
      <nct_id>NCT06021067</nct_id>
    </id_info>
    <brief_title>Dead Mesenchymal Stem Cells for Radiation Lung Injury</brief_title>
    <official_title>Dead Mesenchymal Stem Cells for the Treatment of Radiation Lung Injury</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sichuan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sichuan University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this single center, single arm and prospective study is to explore the safety and&#xD;
        efficacy of hDMSCs in the treatment of radiation pneumonitis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        As a single-center, single-arm, prospective clinical trial, this study aims to explore the&#xD;
        safety and efficacy of hDMSCs in the treatment of radiation pneumonia. This study will&#xD;
        include patients who have received chest radiation therapy and are diagnosed with radiation&#xD;
        lung injury based on clinical manifestations and changes in chest CT imaging. The degree of&#xD;
        lung injury is graded according to CTCAE v5.0 criteria, and the corresponding standard&#xD;
        treatment is received according to its grade. Using the 3+3 design for dose climbing,&#xD;
        according to the order of patient inclusion, the first 3 patients (cohort 1) are treated with&#xD;
        a standard treatment regimen combined with a pre-specified starting dose of dead mesenchymal&#xD;
        stem cells (this study does not set up a live MSC group as a control). There are currently no&#xD;
        relevant research results of previous human trials. The starting dose is obtained by our&#xD;
        preclinical research. The mouse dose is 1×10^5/pc/30g, that is, the effective dose of mice is&#xD;
        3.3×10^6/kg. The dose of mice is 10 times that of humans, and the effective dose of humans is&#xD;
        3.3×10^5/kg. Therefore, the clinical effective dose of 60kg patients is 2.0×10^7, infusion&#xD;
        every 3 days, continuous infusion 4 times, treatment duration of 4~6 weeks. During the&#xD;
        dose-limited toxicity (DLT) observation period (30 days), observe the number of cases of DLT&#xD;
        in 3 patients to determine whether to maintain the current dose group or adjust the dose&#xD;
        group. If the dose of dead mesenchymal stem cells needs to be increased, the dose is ramped&#xD;
        up by 3 times the starting dose (i.e., the second gradient dose is 6.0×10^7) until the number&#xD;
        of patients in either dose group reaches 6 or the dose group adjustment is not possible. To&#xD;
        determine the optimal therapeutic dose for the treatment of radiation lung injury using death&#xD;
        mesenchymal stem cells in combination with standard therapy. A total of 15 patients were&#xD;
        planned to be included in this study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 10, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 10, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>one-arm study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The number of adverse events</measure>
      <time_frame>up to 1 year</time_frame>
      <description>The number of adverse events occurring within a given time frame will be reported according to CTCAE v5.0 to assess overall safety.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Chest contrast-enhanced CT will be used to assess changes in lung injury after treatment</measure>
      <time_frame>up to 1 year</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood gas analysis will be performed after 1 month of dead mesenchymal stem cell injection.</measure>
      <time_frame>up to 1 year</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pulmonary function test will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection.</measure>
      <time_frame>up to 1 year</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>6-minute walking tests will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection.</measure>
      <time_frame>up to 1 year</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>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.</measure>
      <time_frame>up to 1 year</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Radiation Lung Injury</condition>
    <arm_group>
      <arm_group_label>Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Death mesenchymal stem cell</intervention_name>
      <description>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.</description>
      <arm_group_label>Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Received chest radiotherapy;&#xD;
  &#xD;
            -  EOCG PS score of 0 to 3 points;&#xD;
  &#xD;
            -  Diagnosis of radiation lung injury by the attending physician, grade 2 to 3 (according&#xD;
               to the CTCAE v5.0 standards);&#xD;
  &#xD;
            -  Main organs function is normal, that meet the following criteria: blood routine&#xD;
               examination (within 7 days of unused hematopoietic growth factors and blood&#xD;
               transfusion) : ANC ≥ 1.5 x 10^9 / L, PLT ≥ 80 x 10^9 / L, HGB ≥ 80 g/L;Biochemical&#xD;
               examination: TBil ≤ 1.5 x ULN (upper limit of normal);ALT or AST ≤ 2.5 x ULN;&#xD;
               Creatinine clearance ≥ 60 mL/min (Cockcroft - Gault formula); Blood coagulation&#xD;
               function: INR or PT ≤ 1.5 x ULN, if the subjects are receiving anticoagulant therapy,&#xD;
               as long as the scope of PT in anticoagulant drugs for it. Heart function examination,&#xD;
               electrocardiogram (ECG) normal or abnormal ECG (by the researchers to determine the&#xD;
               clinical significance). Heart doppler ultrasound assessment: LVEF ≥ 50%;&#xD;
  &#xD;
            -  Radiation lung injury lasts less than 2 months；&#xD;
  &#xD;
            -  Survival expectation ≥6 months;&#xD;
  &#xD;
            -  Signed and dated written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant or lactating women, men and women of childbearing age who are unwilling or&#xD;
               unable to take effective contraceptive measures;&#xD;
  &#xD;
            -  People with a history of chronic bronchitis, emphysema, or cor pulmonale;&#xD;
  &#xD;
            -  History of lung resection surgery;&#xD;
  &#xD;
            -  Tumor progression;&#xD;
  &#xD;
            -  People with severe lung infection;&#xD;
  &#xD;
            -  Uncontrollable severe systemic diseases (e.g., central nervous system, cardiovascular&#xD;
               system, blood system, digestive system, endocrine system, respiratory system,&#xD;
               genitourinary system, immune system, etc.) and psychosis;&#xD;
  &#xD;
            -  Serious cardiovascular events: a period of 6 months in heart failure (NYHA class III&#xD;
               level IV), myocardial infarction, unstable angina, severe arrhythmia, cerebral&#xD;
               infarction, cerebral hemorrhage;&#xD;
  &#xD;
            -  Abnormal liver and kidney function: AST and ALT exceed the upper limit of normal by&#xD;
               2.5 times. Serum creatinine is greater than 1.5 mg/dl in men and 1.4 mg/dl in women;&#xD;
  &#xD;
            -  Co-infection with HIV, Treponema pallidum, tuberculosis, influenza virus, adenovirus&#xD;
               and other respiratory infections;&#xD;
  &#xD;
            -  Hemorrhage or thrombosis, bleeding or anticoagulant drugs;&#xD;
  &#xD;
            -  Combined with cachexia or other organ failure (requiring organ support);&#xD;
  &#xD;
            -  Shock or invasive ventilation;&#xD;
  &#xD;
            -  Combined with pulmonary interstitial pneumonia caused by other reasons or damage, or&#xD;
               lung imaging showed radioactive lung injury diagnosed with pulmonary interstitial&#xD;
               pneumonia or damage before;&#xD;
  &#xD;
            -  Patients who have participated in clinical studies of stem cells;&#xD;
  &#xD;
            -  The investigators believed that there were other reasons why participants were not&#xD;
               suitable for the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhen-Yu Ding, Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sichuan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhen-Yu Ding, Prof</last_name>
      <phone>86-028-85423609</phone>
      <email>dingzhenyu@scu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>West China Hospital</name>
        <address>
          <city>Chengdu</city>
          <state>Sichuan</state>
          <zip>610000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhen-Yu Ding, Prof</last_name>
        <phone>0086288542357</phone>
        <email>dignzhenyu@scu.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
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    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sichuan University</investigator_affiliation>
      <investigator_full_name>Zhen-Yu Ding</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Dead Mesenchymal Stem Cells</keyword>
    <keyword>Radiation Lung Injury</keyword>
    <keyword>Treatment</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Injury</mesh_term>
      <mesh_term>Wounds and Injuries</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06021067
  org study id: RLI2023
  nct id: NCT06021067
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: one-arm study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The number of adverse events
  time frame: up to 1 year
  description: The number of adverse events occurring within a given time frame will be reported according to CTCAE v5.0 to assess overall safety.
  measure: Chest contrast-enhanced CT will be used to assess changes in lung injury after treatment
  time frame: up to 1 year
  description: 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.
  measure: Blood gas analysis will be performed after 1 month of dead mesenchymal stem cell injection.
  time frame: up to 1 year
  description: 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.
  measure: Pulmonary function test will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection.
  time frame: up to 1 year
  description: 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.
  measure: 6-minute walking tests will be performed after 1, 2, 3, 6, 12month of dead mesenchymal stem cell injection.
  time frame: up to 1 year
  description: 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.
  measure: 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.
  time frame: up to 1 year
  description: 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.
  arm group label: Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia
  arm group type: Experimental
  description: 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.
  intervention type: Biological
  intervention name: Death mesenchymal stem cell
  description: 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.
  arm group label: Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Zhen-Yu Ding, Prof
  role: Principal Investigator
  affiliation: Sichuan University
  last name: Zhen-Yu Ding, Prof
  phone: 86-028-85423609
  email: dingzhenyu@scu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
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  PMID: 23110436
  responsible party type: Principal Investigator
  investigator affiliation: Sichuan University
  investigator full name: Zhen-Yu Ding
  investigator title: Professor
  mesh term: Lung Injury
  mesh term: Wounds and Injuries
  sharing ipd: No