Active clinical trials for "Graft vs Host Disease"

A study to assess efficacy, safety and pharmacokinetics of a tacrolimus new oral formulation (MR4) in de novo bone marrow transplant recipients

Evaluate the clinical activity of sirolimus in combination with cyclosporine and corticosteroids as first line therapy for the treatment of chronic Graft Versus Host Disease.

To determine the safety of sirolimus tablets in renal allograft recipients in a postmarketing surveillance setting.

This study will evaluate the safety and effectiveness of stem cell transplantation in which the donors T lymphocytes have undergone "selective depletion." Certain patients with cancers of the blood undergo transplantation of donated stem cells to generate new and normally functioning bone marrow. In addition to producing the new bone marrow, the donor's T-lymphocytes also fight any tumor cells that might have remained in the body. This attack on tumor cells is called a "graft-versus-leukemia" (GVL) effect. However, another type of T-lymphocyte from the donor may cause what is called "graft-versus-host-disease" (GVHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to reject them. Selective depletion is a technique that was developed to remove the T-lymphocytes that cause harmful GVHD, while keeping those that produce the desirable GVL effect.

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of busulfan and melphalan followed by donor bone marrow transplantation in treating patients who have advanced hematologic cancer.

The purpose of this study is to determine whether extracorporeal photoimmune therapy with UVADEX (ECP) added to standard therapy is effective in the treatment of chronic graft-versus-host disease (GvHD).

Allogeneic peripheral blood stem cell transplantation (PBSCT) is primarily limited by graft-versus-host disease (GVHD). In murine models, we have demonstrated that donor CD4+ T cells of Th1 cytokine phenotype (defined by their secretion of IL-2 and IFN-gamma) mediate GVHD. In contrast, donor CD4+ T cells of Th2 phenotype (defined by their secretion of IL-4, IL-5, and IL-10) do not generate GVHD, and abrogate Th-1-mediated GVHD. Importantly, we have demonstrated that enrichment of murine allografts with Th2 cells reduces GVHD without impairing the ability of donor T cells to prevent graft rejection. These studies indicate that the administration of Th2 cells after allogeneic transplantation represents a strategy for achieving alloengraftment with reduced GVHD. In addition to GVHD, allogeneic PBSCT has been limited by the toxicity associated with conventional myeloablative preparative regimens. Such regimens, which typically utilize total body irradiation (TBI) and high-dose chemotherapy, were once considered essential for the prevention of graft rejection. However, recent clinical studies have shown that non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. In murine models, we have demonstrated that severe host T cell depletion induced by combination fludarabine and cytoxan can prevent even fully-MHC mismatched marrow graft rejection. Although non-myeloablative regimens may reduce regimen-related toxicity, such transplants have been associated with a 30 to 40% incidence of severe acute GVHD that is similar to rates observed with myeloablative regimens. Because non-myeloablative regimens appear to be associated with reduced regimen-related toxicity, we have elected to conduct this phase I study of Th2 cells in the setting of an immunoablative (non-myeloablative) preparative regimen. Patients with leukemia in clinical remission, and patients with refractory lymphoid malignancy will be candidates for this HLA-matched allogeneic PBSCT protocol. Patients will receive novel induction regimen (fludarabine and EPOCH) and transplant preparative regimen (fludarabine and cytoxan) designed to maximally deplete host immune T cells capable of mediating graft rejection. After induction and preparative regimen chemotherapy, patients will receive an unmanipulated, G-CSF mobilized PBSC graft. In the initial six patients receiving this transplant procedure at the NCI, graft rejection has been successfully prevented (100% donor chimerism by day 30 post-transplant). Importantly, GVHD has been observed in all six patients, with three of the six patients developing severe GVHD (grade III). Given that this regimen successfully achieves donor engraftment, and is associated with significant GVHD, this transplant regimen represents an excellent clinical setting for the evaluation of Th2 cells. Using this non-myeloablative allogeneic PBSCT approach, we will perform a Phase I study to evaluate the safety and feasibility of administering donor Th2 cells on day 1 post-transplant. Prior to transplantation, donor CD4+ T cells will be stimulated in vitro using culture conditions that support the generation of donor CD4 cells of the Th2 cytokine profile. If this Phase I study demonstrates that Th2 cell administration is safe and feasible, a Phase III study will be performed to evaluate whether Th2 cell administration reduces the incidence and severity of GVHD. Successful implementation of this Th2 strategy will greatly reduce the morbidity and mortality associated with allogeneic PBSCT, and may also represent an approach to stem cell transplantation in patients lacking an HLA-matched donor.

Cancers of the blood, sometimes referred to as hematologic malignancies, are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow. These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms. The disease is life threatening because it blocks the normal function of the marrow, which is to produce red cells (preventing anemia), white cells (preventing infection), and platelets (preventing progression). Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies. However, BMT is a complicated procedure and can be associated with dangerous side effects. In this study researchers are attempting to find ways to reduce the complications of BMT, so that it would be possible to use it more safely and can be offered more patients. In order to do this, researchers are developing new techniques to make BMT safer. It requires making small changes to the standard procedure, which may improve the outcome. The experimental procedures researchers are evaluating are: <TAB>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation <TAB> Cyclosporine given immediately after the transplant <TAB>Add-back of donor lymphocytes Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur. Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies.

RATIONALE: Cyclosporine may induce graft-versus-host disease and make the body build an immune response that will kill cancer cells. Interleukin-2 and interferon gamma may enhance the effectiveness of graft-versus-host disease to kill cancer cells. PURPOSE: Randomized phase III trial to determine the effectiveness of graft-versus-host disease in treating patients who have recurrent or refractory lymphoma or Hodgkin's disease .

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.