A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells

NCT02277145 | Completed Phase 1

• 1 other identifier: CAS-XDA001-SH/IGDB
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-radiotherapy Pulmonary Fibrosis

Keywords

radiation-induced pulmonary fibrosis; MSCs

Outcome Measures

Primary Outcomes (2)

• 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.

  6 months

• 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.

  6 months

Secondary Outcomes (24)

• Clinical Indicator 1: change in blood gas analysis

  3-6 months

• Clinical Indicator 2: change in pulmonary function analysis

  3-6 months

• Clinical Indicator 3: 6-minute walk test distance

  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

Study Arms (1)

treatment group

EXPERIMENTAL

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

Biological: clinical grade umbilical cord mesenchymal stem cells

Interventions

clinical grade umbilical cord mesenchymal stem cells BIOLOGICAL

10\^6 (1 million) /Kg/person cells of clinical grade umbilical cord MSCs will be injected after fully lavage of the localized lesions

treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jianwu Dai: lead
• Southwest Hospital, China: collaborator

Study Sites (1)

First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)

Chongqing, Chongqing Municipality, 400038, China

Location

Study Officials

• JianWu Dai, Ph.D

  Chinese Academy of Sciences

  PRINCIPAL INVESTIGATOR

• Wei Xiong, M.D

  First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)

  STUDY CHAIR

• Xiaotian Dai, M.M

  First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator of Regenerative Medicine Laboratory, Institute of Genetics and Developmental Biology, CAS

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 28, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: July 24, 2019

Record last verified: 2018-07

Locations

CN (1)