Mesenchymal Stem Cell Therapy for Lung Rejection
Condition: Lung Transplant Reject; Bronchiolitis Obliterans
MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Bronchiolitis Obliterans Syndrome
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Mesenchymal stem cell 0.5; Mesenchymal stem cell 1.0
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bronchiolitis obliterans; lung transplant; mesenchymal stem cell; cell therapy