View clinical trials related to Severe Aplastic Anemia.
Filter by:This is a single arm, phase I study to assess the tolerability of abatacept when combined with cyclosporine and mycophenolate mofetil as graft versus host disease prophylaxis in children undergoing unrelated hematopoietic stem cell transplant for serious non-malignant diseases as well as to assess the immunological effects of abatacept. Participants will be followed for 2 years.
Hematopoietic progenitor cell (HPC- primitive cells in the blood, bone marrow and umbilical cord that can restore the bone marrow) transplant can be a curative therapy for the treatment of hematologic malignancies (a disease of the bone marrow and lymph nodes). The source of cells used for the transplant comes from related (sibling) and in cases where there is no sibling match, from unrelated donors through the National Marrow Donor Program. The availability of a suitable donor can be a significant obstacle for patients who need a transplant but do not have a matched donor. Cord blood that has been harvested from an umbilical cord shortly after birth has a rich supply of cells needed for transplant. These stored cord bloods are now being used to transplant adults without a matched donor Advantages to using cord blood includes a readily available source of cells with no risk to the donor during the collection process, immediate source of cells in urgent situations (no lengthy donor work-up)and a reduction in infectious disease transmission to the recipient. One of the main disadvantages is the cord blood has a small number of cells needed for transplant. In an adult, usually two cords are needed and large recipients do not qualify because they need too many cells. This study will use two different preparative regimens (chemotherapy and radiation) followed by one or two umbilical cord units (UBC). The preparative regimen used will be chosen by the physician and is based on patient's age, disease and medical condition at the time of transplant. Multiple objectives for this study include disease-free and overall survival, treatment related mortality, rate of cells taking hold, and the incidence and severity of the transplant complication called graft versus host disease (GVHD).
The investigators hypothesis is that eltrombopag given to patients with moderate to very severe aplastic anemia will result in an increase in platelet counts. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, treatment with eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer bleeding events. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, eltrombopag will have an acceptable toxicity rate <3%, at doses that result in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag levels in peripheral blood will correlate with improved platelet counts.
The purpose of this clinical trial is to investigate the safety of human placental-derived stem cells (HPDSC) given in conjunction with umbilical cord blood (UCB) stem cells in patients with various malignant or nonmalignant disorders who require a stem cell transplant. Patients will get either full dose (high-intensity) or lower dose (low intensity) chemo- and immunotherapy followed by a stem cell transplantation with UCB and HPDSC.
The purpose of this study is to provide an opportunity for patients with malignancies or bone marrow failure states who lack a suitable sibling donor to undergo allogeneic hematopoietic progenitor cell transplantation using cells from unrelated individuals or cord blood registries.
Background: - Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in low blood cell counts, which require frequent transfusions. Standard treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). This regimen has been shown to improve the blood counts in about two-thirds of patients. However, the ATG/CsA regimen has the following limitations: (a) the disease can come back (relapse) in about one-third of patients who improve initially; and (b) in about 10% to 15% of cases, certain types of bone marrow cancer (such as myelodysplasia and leukemia) can develop (called evolution). Experience with other drugs in SAA such as cyclophosphamide suggests that similar response rates to ATG/CsA can be achieved with a lower risk of relapse and clonal evolution. However, cyclophosphamide was found to have significant side effects in SAA when investigated over 10 years ago due to increase risk of fungal infections. - Better antibiotic drugs against fungus have been developed and are widely used to treat patients who have low white blood cell counts and are at risk of developing infections. In SAA patients in particular, these newer antibiotics have had a large impact in preventing and treating fungus infections. Researchers are revisiting the use of cyclophosphamide in SAA treatment, and plan to give a lower dose of CsA in combination with the immune-suppressing drug cyclophosphamide, as well as antibiotics to protect against infections, as a possible treatment for the disease. Objectives: - To determine the safety and effectiveness of the combination of cyclophosphamide and cyclosporine in treating severe aplastic anemia that has not been treated with immunosuppressive therapy.
Background: - Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in low blood cell counts, which require frequent transfusions. Standard initial treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). Patients with SAA who do not respond to initial treatment with ATG (refractory) have a high risk of dying without additional treatment. In these cases, for those who do not have a matched bone marrow transplant donor there is no well-defined standard therapy. In our experience with patients who do not respond to horse ATG + CsA, only about one-third of patients who are re-treated with rabbit ATG + CsA improve. Experience with cyclophosphamide in the treatment of refractory severe aplastic anemia suggests that this drug is able to improve blood counts in about 50% of cases. However, the cyclophosphamide regimen has been associated with a significant infection risk (mostly caused by fungus) in studies conducted over 10 years ago due to the lowering of the white blood cell levels. - Better antibiotic drugs against fungus have been developed and are widely used to treat patients who have low white blood cell counts and are at risk of developing infections. In SAA patients in particular, these newer antibiotics have had a large impact in preventing and treating fungus infections. Researchers are revisiting the use of cyclophosphamide at lower doses to minimize its side effects given in combination with another immune suppressant, fludarabine. Objectives: - To determine the safety and effectiveness of the combination of fludarabine plus cyclophosphamide in treating severe aplastic anemia that has not responded to initial treatments.
The primary objective of this study is to assess the safety and efficacy of performing unrelated stem cell transplants using intravenous busulfan and fludarabine as preparative therapy and tacrolimus plus methotrexate as the GVHD prophylaxis regimen. The goal is to demonstrate safety, aiming for a transplant related mortality rate (TRM) of < or equal to 40% at 100 days. A TRM of > or equal to 60% will be considered unacceptable. Another goal is to demonstrate efficacy by showing and overall survival of >40% at 1-year following transplant.
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation and immunosuppressive treatment with anti-thymocyte globulin (ATG) and cyclosporine (CsA) have dramatically changed the natural course of this illness, with 5 year survival of 75% in patients undergoing either treatment. Since most patients are not suitable candidates for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a histocompatible sibling, efforts at NHLBI have focused on improving immunosuppression treatment in order to improve response rates, survival, and to decrease relapse. In our experience of 122 patients treated at NHLBI with the combination of ATG and cyclosporine, one quarter to one third did not respond; about 50% of responders relapsed; and 5 year survival was correlated with the robustness in blood cell count improvement at 3 months (reticulocyte or platelet count greater than or equal to 50,000 /uL). Why some patients do not respond initially while others relapse is unclear. Autoreactive T cells may be resistant to the effect of ATG/CsA (nonresponders), while in others residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel immunosuppressive regimens to increase response rates and hematologic recovery at 3 months and to decrease relapse rates are needed. An ongoing NHLBI trial, which is close to completing accrual, has added mycophenolate mofetil (MMF) for a total of 18 months to standard ATG + CsA in an attempt to reduce the relapse rate after cyclosporine is discontinued. Preliminary results have been disappointing, with no marked reduction in relapse among patients who received MMF. Sirolimus (rapamycin, Rapamune , RAPA) is a novel immunosuppressive agent, which acts synergistically with cyclosporine by blocking T cell activation through CsA-resistant pathways. The potentiation of the combination of CsA-RAPA has been established in vitro and in the clinical setting, mainly in islet cell and solid organ transplantation. The significant increase in response rate seen with the addition of CsA to ATG indicated that an inhibitory effect on T lymphocytes is important in blocking autoreactive T cells in aplastic anemia. The combination of CsA-RAPA may further block activated autoreactive T cells and therefore lead to improved response rates (and survival) and decreased relapse rates. This prospective randomized phase II study will investigate two different immunosuppressive regimens in patients with severe aplastic anemia who have not received prior immunosuppressive therapy. One arm will receive ATG + CsA in addition to sirolimus for 6 months, and the second arm will receive standard ATG + CsA for 6 months followed by a slow taper of CsA with a 25% dose reduction every 3 months for the subsequent 18 months. This trial will determine the effectiveness of sirolimus in patients with aplastic anemia as well as the role of a cyclosporine taper in preventing relapses. Primary endpoint will be no longer meeting criteria for severe aplastic anemia while secondary endpoints are relapse, robustness of hematologic recovery at 3 months, survival, clonal evolution to PNH, myelodysplasia and acute leukemia. 10/11/2005. The Sirolimus (Rapamune) arm of the trial was stopped for lack of efficacy. The study will continue as a single arm study to establish if slow taper of CsA prevents relapse rates after initial standard treatment with ATG followed by CsA for six months.
RATIONALE: Although used primarily to treat malignant disorders of the blood, allogeneic stem cell transplantation can also cure a variety of non-cancerous, inherited or acquired disorders of the blood. Unfortunately, the conventional approach to allogeneic stem cell transplantation is a risky procedure. For some non-cancerous conditions, the risks of this procedure outweigh the potential benefits. This protocol is designed to test a new approach to allogeneic stem cell transplantation. It is hoped that this approach will be better suited for patients with non-cancerous blood and bone marrow disorders.