Lung Transplant RejectPhase 1NCT02181712
Mesenchymal Stem Cell Therapy for Lung Rejection
A Phase 1 study testing Mesenchymal stem cell 0.5 and Mesenchymal stem cell 1.0 in people with Lung Transplant Reject and Bronchiolitis Obliterans, run by Mayo Clinic at 1 site in United States.
Trial summary
To assess the safety and feasibility of mesenchymal stem cells therapy in patients with transplant related bronchiolitis obliteran syndrome (BOS) Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Transplant Reject, Bronchiolitis Obliterans
- What is being tested?
- Mesenchymal stem cell 0.5 and Mesenchymal stem cell 1.0
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to 12 Aug 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
To assess the safety and feasibility of mesenchymal stem cells therapy in patients with transplant related bronchiolitis obliteran syndrome (BOS)
Read the 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.
- Conditions
- Lung Transplant Reject, Bronchiolitis Obliterans
- Being tested
- Mesenchymal stem cell 0.5, Mesenchymal stem cell 1.0
- Keywords
- Bronchiolitis obliterans, lung transplant, mesenchymal stem cell, cell therapy
- Medical subject headings
- Bronchiolitis Obliterans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stem cell 0.5Biological
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.
Mesenchymal stem cell 1.0Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal Stem cells | Experimental | Subjects who have never received Mesenchymal Stem Cells Receives: Biological: Mesenchymal stem cell 0.5; Biological: Mesenchymal stem cell 1.0 |
| Booster Mesenchymal Stem Cells | Experimental | Subjects who have previously received Mesenchymal Stem Cells Receives: Biological: Mesenchymal stem cell 1.0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 weeks
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.
Measured: Up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2014 (estimated)
- Study startJul 2014
- Primary completion12 Aug 2021
- Study completion12 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Transplant RejectStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David B. Erasmus, Mayo Clinic
- Investigators
- David Erasmus, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02181712
- Sponsor's protocol ID
- 14-000025
- Status last verified
- Oct 2021
- First submitted
- 2 Jul 2014
- Last updated
- 7 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02181712
- Acronym / sponsor ID
- 14-000025
- Conditions
- Lung Transplant Reject, Bronchiolitis Obliterans
- Keywords
- Bronchiolitis obliterans, lung transplant, mesenchymal stem cell, cell therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Jul 2014 (actual)
- Primary completion
- 12 Aug 2021 (actual)
- Study completion
- 12 Aug 2021 (actual)
- First posted
- 4 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stem cells | Experimental | Biological: Mesenchymal stem cell 0.5, Biological: Mesenchymal stem cell 1.0Subjects who have never received Mesenchymal Stem Cells |
| Booster Mesenchymal Stem Cells | Experimental | Biological: Mesenchymal stem cell 1.0Subjects who have previously received Mesenchymal Stem Cells |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal stem cell 0.50.5 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. | Biological | Mesenchymal Stem cells |
| Mesenchymal stem cell 1.01 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. | Biological | Booster Mesenchymal Stem Cells, Mesenchymal Stem cells |
Primary outcome
Number of Participants with serious and non-serious adverse events
Time frame: Up to 2 weeks
Patients will be assessed for their capacity to tolerate IV infusion of MSC without acute clinical or physiological deterioration.
Changes in pulmonary function tests
Time frame: Up to 2 weeks
Vital signs, pulmonary function tests (FEV1 and FCV) and Borg Dyspnea Index will be evaluated. Chest Radiograph, CBC and serum chemistry will be performed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Erasmus, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesenchymal stem cell 0.5 and Mesenchymal stem cell 1.0 in people with Lung Transplant Reject and Bronchiolitis Obliterans, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with serious and non-serious adverse events (time frame: Up to 2 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.