Induction of Donor Specific Tolerance in Recipients of Cardiac Allografts by Donor Stem Cell Infusion
Condition: Heart Transplantation
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of this research study is to establish chimerism and avoid graft-versus-host disease
      in patients who need a heart transplant.
    

Detailed description: 
      At the present time, heart transplant recipients must take anti-rejection medication to
      prevent rejection of the donated heart. Even with this medication, chronic rejection is the
      most common cause of late graft loss. The anti-rejection agents themselves are significantly
      toxic, with side effects including kidney damage, infection and an increased incidence of
      cancer. The goal of this study is to allow the patient to develop "tolerance" to the
      transplanted heart while maintaining a competent immune system. Tolerance enables the
      transplant recipient's body to recognize the transplanted organ as self rather than foreign
      tissue. The recipient will not try to reject the donor heart and the need for anti-rejection
      medication could be dramatically decreased or eliminated entirely. To accomplish this,
      patients in this study will receive specially treated bone marrow taken from their heart
      donor. Bone marrow transplant has been shown in animal studies and in humans to induce
      tolerance following organ transplant.

      Two factors limit the application of donor marrow transplant to induce tolerance: 1)
      preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD).
      Traditional conditioning destroys the recipient's immune system and requires that the marrow
      transplant be successful because the patient is unable to fight off infection if the donor
      cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as
      foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new
      approach to conditioning which leaves the patient's immune system intact. The transplant
      product is depleted of GVHD-producing cells but retains tolerance-promoting facilitating
      cells, which are intended to ensure the donor and recipient cells coexists peacefully, a
      state called mixed chimerism. The toxicity of conditioning and transplantation is
      significantly reduced.

      In this study, we will determine the appropriate cell dose to safely establish mixed
      chimerism following partial conditioning in heart transplant recipients. The study takes a
      gradual approach to increasing the cell dose to achieve mixed chimerism. We believe this
      study will provide a breakthrough in the approach to heart transplantation. Our goal is to
      evaluate the potential of safely establishing mixed chimerism to induce tolerance following
      heart transplant and reduce or eliminate the need for anti-rejection therapy.
    

Intervention name(s): enriched hematopoetic stem cell infusion
Intervention type(s): Biological
Intervention description(s): Enriched Hematopoetic Stem Cell Infusion
Intervention model: Single Group Assignment
Intervention model description: Open label
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Marrow/hematopoietic stem cell transplant