Overview

This trial is active, not recruiting.

Conditions lung transplant reject, bronchiolitis obliterans
Treatment mesenchymal stem cell
Phase phase 1
Sponsor Mayo Clinic
Start date July 2014
End date July 2017
Trial size 9 participants
Trial identifier NCT02181712, 14-000025

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
2- 4 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

Primary Outcomes

Measure
Number of Participants with serious and non-serious adverse events
time frame: Up to 2 weeks
Changes in pulmonary function tests
time frame: Up to 2 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria 1. Age range: 18 - 75 years 2. Gender: Male of female 3. Target disease or condition: Lung transplant recipients with treatment refractory moderate BOS. Patient must have diagnosis of treatment refractory BO/BOS Subject must have had, for each of the following three (3) treatment categories, either an inadequate or lost response (recurrence or persistence of symptoms) to a drug in that category within the past 24 months or documented intolerance to a drug in that category at any time. Note that subject may currently be receiving steroids or immunomodulators (see dosage requirements below) at the time of enrollment. 4. Enhanced steroid therapy 5. Enhanced immunosuppression 6. Trial/failure to other therapies like Azythromycin, anti-reflux therapy and others. 7. 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. 8. Subject must have adequate renal function; calculated creatinine clearance of greater than 30 ml/min. 9. Subject must be available for all specified assessments at the study site through the completion of the study. 10. Subject must provide written ICF and authorization for use of and disclosure of PHI. Exclusion Criteria 1. 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 2. Evidence or history of malignancy 3. Evidence or history of autoimmune disorders independent of BO/BOS 4. Pregnant or breast-feeding 5. Positive screening for HIV Hepatitis B and Hepatitis C 6. 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. 7. Evidence of significant cardiac dysfunction 8. Septicemia with high fever and hemodynamic instability 9. History of CMV pneumonitis 10. Patients who received any experimental therapy (drug or biologic) for any indication within 3 months of the study enrollment

Additional Information

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 Lung Rejection
Principal investigator Cesar Keller, MD
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 9 subjects (3 subjects in each of dose escalating subject cohorts). 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Mayo Clinic.