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Mesenchymal Stem Cell Therapy for Lung Rejection

Primary Purpose

Lung Transplant Reject, Bronchiolitis Obliterans

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Mesenchymal stem cell 0.5

Mesenchymal stem cell 1.0

About this trial

This is an interventional treatment trial for Lung Transplant Reject focused on measuring Bronchiolitis obliterans, lung transplant, mesenchymal stem cell, cell therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Age range: 18 - 75 years
Gender: Male of female
Target disease or condition: Lung transplant recipients with treatment refractory moderate to severe o-CLAD. Patient must have diagnosis of treatment refractory o-CLAD Subject must have failed a standard immunosuppression regimen for lung transplant recipients. Note that subject may currently be receiving steroids or immunomodulators (see dosage requirements below) at the time of enrollment.
The patient has persistent symptoms of BOS despite trials of other agents such asAzythromycin, anti-reflux therapy and others.
Informed consent form (ICF): Each patient will be required to sign an IRB approved ICF. Only subjects who have signed the ICF will be enrolled into the study. The ICF will include elements required by Mayo IRB and FDA in US 21CFR50.
Subject must have adequate renal function; estimated glomerular filtrate rate of greater than 30 ml/min.
Subject must be available for all specified assessments at the study site through the completion of the study.
Subject must provide written ICF and authorization for use of and disclosure of PHI.

Exclusion Criteria

Patients with clinically significant illness with manifestations of significant organ dysfunction which in the judgment of the PI or co-investigator would render the study subject unlikely to tolerate the MSC infusion or complete the study
Patient should not have cancer not deemed to be in remission. (Superficial skin cancer shall not be deemed an exclusion criteria)Evidence or history of autoimmune disorders independent of o-CLAD
Pregnant or breast-feeding
Positive screening for HIV Hepatitis B and Hepatitis C
Evidence of liver dysfunction; Liver profile showing alkaline phosphatase higher than 345 u/L, total bilirubin greater than 1.65 mg/dL, ALT greater than 275 units/L and AST great than 240 units/L.
Evidence of significant cardiac dysfunction
Septicemia with high fever and hemodynamic instability
History of CMV pneumonitis
Patients who received any experimental therapy (drug or biologic) for any indication within 12 months of the study enrollment

Sites / Locations

Mayo Clinic in Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Mesenchymal Stem cells

Booster Mesenchymal Stem Cells

Arm Description

Subjects who have never received Mesenchymal Stem Cells

Subjects who have previously received Mesenchymal Stem Cells

Outcomes

Primary Outcome Measures

Number of Participants with serious and non-serious adverse events

Patients will be assessed for their capacity to tolerate IV infusion of MSC without acute clinical or physiological deterioration.

Changes in pulmonary function tests

Vital signs, pulmonary function tests (FEV1 and FCV) and Borg Dyspnea Index will be evaluated. Chest Radiograph, CBC and serum chemistry will be performed.

Secondary Outcome Measures

Full Information

NCT ID

NCT02181712

First Posted

July 2, 2014

Last Updated

October 5, 2021

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT02181712

Brief Title

Mesenchymal Stem Cell Therapy for Lung Rejection

Official Title

A Pilot Study to Evaluate the Safety and Feasibility of Mesenchymal Stem Cells to Induce Remission in Lung Transplant Patients Experiencing Treatment-refractory Moderate to Severe Lung Rejection

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

July 2014 (Actual)

Primary Completion Date

August 12, 2021 (Actual)

Study Completion Date

August 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

To assess the safety and feasibility of mesenchymal stem cells therapy in patients with transplant related bronchiolitis obliteran syndrome (BOS)

Detailed Description

The overall clinical development strategy of this project is to conduct this Phase I dose escalation study entitled "A pilot Study to Evaluate the Safety and Feasibility of Mesenchymal Stem Cells to Induce Remission in Lung Transplant Patients Experiencing Treatment-Refractory Moderate Lung Rejection". This study will be performed under this current IND application and will be limited to the proposed 19 subjects (5 subjects in each of two dose escalating subject cohorts, and 5 subjects in a "boost dose" group who previously received MSC as part of the previous phase 1a study which included 9 patients In this application we are proposing to evaluate safety and feasibility of allogeneic, bone marrow (BM) derived mesenchymal stem cells (MSC) to induce remission of moderate treatment refractory bronchiolitis obliterans (BO/BOS). Lung transplant patients with treatment refractory BO/BOS (grade 3) who do not qualify for a second transplant have near 100% mortality or extreme disability. MSCs are multi-potent cells that have the capacity to induce tissue repair and modulate immune response. They have been used successfully in preclinical and clinical studies to treat graft versus host disease (GVHD) and inflammatory bowel disease. Patients that progressed to moderate BO despite adequate medical treatments and who do not qualify for a second transplant will receive intravenous treatments of allogeneic MSC. The safety measure will include tolerance of MSC infusion and absence of significant cardiopulmonary compromise. The feasibility assessment will include ease of recruitment, practical issue of transporting, preparing and infusing the MSCs. The clinical assessment from this initial safety study is intended to demonstrate safety of human MSC in subjects with BO and to evaluate the cell dose that demonstrates signs of efficacy. Pending favorable safety results and pharmacokinetic and pharamcodynamic data obtained in the current proposed study we will likely conduct additional human studies with a more directed focus on the evaluation of efficacy while collecting additional safety information.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Transplant Reject, Bronchiolitis Obliterans

Keywords

Bronchiolitis obliterans, lung transplant, mesenchymal stem cell, cell therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mesenchymal Stem cells

Arm Type

Experimental

Arm Description

Subjects who have never received Mesenchymal Stem Cells

Arm Title

Booster Mesenchymal Stem Cells

Arm Type

Experimental

Arm Description

Subjects who have previously received Mesenchymal Stem Cells

Intervention Type

Biological

Intervention Name(s)

Mesenchymal stem cell 0.5

Intervention Description

0.5 million MSC per Kg will be infused intravenously. Product will be infused at the rate of 2 - 3 ml/minute during the first 15 minutes and may be adjusted up to 5ml/minutes if tolerable. It is anticipated that the infusion will be completed within approximately 3 hours.

Intervention Type

Biological

Intervention Name(s)

Mesenchymal stem cell 1.0

Intervention Description

1 million MSC per Kg will be infused intravenously. Product will be infused at the rate of 2 - 3 ml/minute during the first 15 minutes and may be adjusted up to 5ml/minutes if tolerable. It is anticipated that the infusion will be completed within approximately 3 hours.

Primary Outcome Measure Information:

Title

Number of Participants with serious and non-serious adverse events

Description

Patients will be assessed for their capacity to tolerate IV infusion of MSC without acute clinical or physiological deterioration.

Time Frame

Up to 2 weeks

Title

Changes in pulmonary function tests

Description

Vital signs, pulmonary function tests (FEV1 and FCV) and Borg Dyspnea Index will be evaluated. Chest Radiograph, CBC and serum chemistry will be performed.

Time Frame

Up to 2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Age range: 18 - 75 years Gender: Male of female Target disease or condition: Lung transplant recipients with treatment refractory moderate to severe o-CLAD. Patient must have diagnosis of treatment refractory o-CLAD Subject must have failed a standard immunosuppression regimen for lung transplant recipients. Note that subject may currently be receiving steroids or immunomodulators (see dosage requirements below) at the time of enrollment. The patient has persistent symptoms of BOS despite trials of other agents such asAzythromycin, anti-reflux therapy and others. Informed consent form (ICF): Each patient will be required to sign an IRB approved ICF. Only subjects who have signed the ICF will be enrolled into the study. The ICF will include elements required by Mayo IRB and FDA in US 21CFR50. Subject must have adequate renal function; estimated glomerular filtrate rate of greater than 30 ml/min. Subject must be available for all specified assessments at the study site through the completion of the study. Subject must provide written ICF and authorization for use of and disclosure of PHI. Exclusion Criteria Patients with clinically significant illness with manifestations of significant organ dysfunction which in the judgment of the PI or co-investigator would render the study subject unlikely to tolerate the MSC infusion or complete the study Patient should not have cancer not deemed to be in remission. (Superficial skin cancer shall not be deemed an exclusion criteria)Evidence or history of autoimmune disorders independent of o-CLAD Pregnant or breast-feeding Positive screening for HIV Hepatitis B and Hepatitis C Evidence of liver dysfunction; Liver profile showing alkaline phosphatase higher than 345 u/L, total bilirubin greater than 1.65 mg/dL, ALT greater than 275 units/L and AST great than 240 units/L. Evidence of significant cardiac dysfunction Septicemia with high fever and hemodynamic instability History of CMV pneumonitis Patients who received any experimental therapy (drug or biologic) for any indication within 12 months of the study enrollment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Erasmus, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Florida

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

12. IPD Sharing Statement

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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Mesenchymal Stem Cell Therapy for Lung Rejection

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