A Study to Evaluate the Potential of Mesenchymal Stromal Cells to Treat Obliterative Bronchiolitis After Lung Transplantation

Study Overview
=================
Brief Summary
-----------------
The primary aim of this study is to establish the safety of infusions of Mesenchymal Stromal Cells (MSC) from related or unrelated Human Leukocyte Antigen (HLA) identical or HLA mismatched donors in the management of bronchiolitis obliterans syndrome after lung transplantation.

Official Title
-----------------
A Study to Evaluate the Potential of Mesenchymal Stromal Cells to Treat Obliterative Bronchiolitis After Lung Transplantation

Conditions
-----------------
Bronchiolitis Obliterans, Lung Transplantation

Intervention / Treatment
-----------------
* Other: MSC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with single, bilateral or heart-lung allografts Patients with bronchiolitis obliterans syndrome (BOS) grades 2 & 3 (defined and graded according to international criteria (Appendix 1)), with evidence of deterioration in allograft function (i.e. deteriorating FEV1 or worsening BOS grade) within the last 12 months. Patients with BOS grade 1 and evidence of deterioration in allograft function (i.e. deteriorating FEV1 or worsening BOS grade) within the last 12 months and at least one of the following additional risk factors for subsequent death: Single lung transplant Rapid deterioration (>20% fall in FEV1 in the previous 12 months) A pre-transplant diagnosis of usual interstitial pneumonia (pulmonary fibrosis) or pulmonary hypertension Exclusion Criteria: Patients with active infection, acute allograft rejection, or airway anastomotic complications Patients with > 3 infective exacerbations of BOS in the last 12 months Patients with a history of cytomegalovirus (CMV) pneumonitis Patients with poor performance status and/or not expected to survive 3 months Patients who are pregnant or breastfeeding Patients with an allergy to beef products. Any condition that in the opinion of the Investigator may interfere with the safety of the patient, his / her completion of required follow-up visits or evaluation of the study objectives.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC<br> | Other: MSC<br>* mesenchymal stromal cells (MSC), aiming for 2 x 106 /kg cells recipient body weight, aiming for a frequency of twice weekly for two weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the safety of infusions of MSC from related or unrelated HLA identical or HLA mismatched donors in the management of bronchiolitis obliterans syndrome after lung transplantation. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To document changes in lung function and 6 minute walk distance (6MWD) following infusion of MSC |  | 12 months | 
| To document survival post MSC infusion |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mesenchymal stromal cells, Bronchiolitis obliterans, Lung transplant