Dead Mesenchymal Stem Cells for Radiation Lung Injury

August 31, 2023 updated by: Zhen-Yu Ding, Sichuan University

Dead Mesenchymal Stem Cells for the Treatment of Radiation Lung Injury

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Recruiting
        • West China Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Death mesenchymal stem cell therapy plus standard treatment for radiation pneumonia
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of adverse events
Time Frame: up to 1 year
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
Time Frame: up to 1 year
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.
Time Frame: up to 1 year
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.
Time Frame: up to 1 year
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.
Time Frame: up to 1 year
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.
Time Frame: up to 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sichuan University

Investigators

  • Principal Investigator: Zhen-Yu Ding, Prof, Sichuan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 10, 2023

Primary Completion (Estimated)

September 10, 2024

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

June 24, 2023

First Submitted That Met QC Criteria

August 31, 2023

First Posted (Actual)

September 1, 2023

Study Record Updates

Last Update Posted (Actual)

September 1, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RLI2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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