Bone Marrow Stromal Cell Infusions for Stem Cell Transplant Complications
Condition: Graft-Versus-Host Disease
MeSH terms: Graft vs Host Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Bone marrow stromal cells (BMSC) from bone marrow biopsies can be used to treat
           disorders that cause inflammation and immune system diseases. BMSC have been used to
           treat graft versus host disease (GVHD), a complication that can develop after stem cell
           transplants. BMSC have also been used to treat other post-transplant complications, like
           marrow failure or tissue injury.

        -  The National Institutes of Health (NIH) has developed a procedure for collecting and
           preserving BMSC from volunteer donors. These donors have passed tests to ensure that
           their cells are healthy enough to be used for treatment. Researchers want to use the
           collected cells to treat people with GVHD, marrow failure, or tissue injury following
           stem cell transplants.

      Objectives:

      - To test the safety and effectiveness of NIH-collected BMSC to treat complications from stem
      cell transplants.

      Eligibility:

        -  Individuals between 18 and 75 years of age who have complications from stem cell
           transplants.

        -  Complications are acute GVHD, poor bone marrow function, or tissue or organ damage.

      Design:

        -  Participants will be screened with a physical exam and medical history. They will also
           have imaging studies and blood tests.

        -  Participants will provide blood, skin, and bone marrow samples before the BMSC
           treatment. Additional samples, including tissue samples, will be collected after the
           start of treatment.

        -  Participants will have up to three BMSC infusions. There will be a week between each
           infusion. Participants will be monitored closely during each infusion. Any side effects
           will be treated.

        -  Treatment will be monitored with frequent blood tests and physical exams.

        -  After the end of the infusions, participants will have regular followup visits for up to
           2 years.
    

Detailed description: 
      Bone marrow stromal cells (BMSC) derived from bone marrow aspiration/biopsy have important
      anti-inflammatory and immunosuppressive properties that make them suitable candidates for
      cellular therapy of inflammatory and degenerative disorders. BMSC suppress lymphocyte immune
      responsiveness and can hone in to sites of inflammation and promote healing. BMSC were first
      used in man to successfully treat refractory acute graft versus host disease (aGVHD). A
      recent multicenter study treating refractory aGVHD reported a 66% response rate and a
      sustained survival in responding patients. BMSC are currently being evaluated in acute GVHD
      in several ongoing studies worldwide. BMSC have also been used to treat post-transplant
      conditions not directly due to GVHD. Responses have been reported in hemorrhagic cystitis,
      and pneumoperitoneum. BMSC are also under evaluation in the treatment of inflammatory and
      autoimmune disorders.

      The Cell Processing Section of the Department of Transfusion Medicine at the Clinical Center
      NIH has developed a procedure for collecting, expanding and cryopreserving clinical grade
      BMSC under an FDA Drug Master File (DMF). Marrow will be aspirated from volunteer donors
      participating on protocol 10-CC-0053 who have passed the standard screening for blood and
      marrow donors and BMSC will be expanded in vitro. Since it is not necessary to HLA-match BMSC
      donors with their recipient for this study, a BMSC repository will be used as the source of
      BMSC for this study.

      This will be the first trial of the safety of the NIH BMSC cellular product in stem cell
      transplant recipients. In this phase I study, open to adult NIH allogeneic stem cell
      transplantation (SCT) recipients, we will evaluate the safety of a fixed dose of BMSC
      infusions (target dose of 2 x 106 BMSCs /kg (+/- 10%)) in patients with acute GVHD, marrow
      failure or tissue injury following allogeneic SCT. Up to three BMSC infusions will be given
      every 7 3 days apart. Safety will be monitored continuously with a stopping rule for toxicity
      based on the treatment-related serious adverse event rate. Organ-specific clinical responses
      will be measured. Where possible we will also attempt to identify transfused BMSC in sites of
      damage in biopsy material. It is planned to accrue up to 10 subjects over a 6-month period.
    

Intervention name(s): Bone Marrow Stromal Cell Infusion
Intervention type(s): Procedure
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immune Suppression; BMSC; GVHD; Marrow Failure; Regimen Related Toxicity; Graft-Versus-Host Disease