View clinical trials related to Anemia, Hypoplastic.
Filter by:Background: - Severe plastic anemia can lead to problems with bone marrow platelet production and result in low blood platelet counts, which require frequent platelet transfusions to improve blood clotting. - A standard treatment for SAA involves injections of rabbit-antithymocyte globulin (r-ATG). r-ATG is developed by injecting horses with a type of human white blood cells called thymocytes. The horse's immune system reacts against these cells and makes antibodies that can destroy them. These antibodies are collected and purified to make r-ATG. Horses can also be used for this procedure to make horse-antithymocyte globulin (h-ATG). - h-ATG is approved by the Food and Drug Administration for the treatment of aplastic anemia. h-ATG is a standard first-line method to treat aplastic anemia, but researchers do not know how effective it is in patients who were first treated unsuccessfully with r-ATG. Objectives: - To evaluate the effectiveness and safety of horse-ATG (with cyclosporine) in increasing blood counts and reducing the need for transfusions in aplastic anemia patients who have failed to respond to prior immunosuppressive treatment with rabbit-ATG and cyclosporine. Eligibility: - Patients 2 years of age and older who have consistently low blood platelet counts related to aplastic anemia that has not responded to conventional treatment with rabbit-ATG. Design: - After initial screening, medical history, and blood tests, patients will be admitted to the inpatient unit at the National Institutes of Health Clinical Center. Researchers will perform a skin test with h-ATG to check for allergic or other adverse reaction. - After the skin test, h-ATG will be given into a vein continuously over 4 days. - Cyclosporine will also be given to improve the response rate of ATG treatment. Treatment with cyclosporine will start the same day as the h-ATG, either in liquid or capsule form, and continued for 6 months. The dose of cyclosporine will be monitored and adjusted based on blood levels and signs of side effects in the kidney and liver. - To prevent or treat infections that may result from cyclosporine s effect on the immune system, patients will also take inhaled or capsule doses of pentamidine. - After the study is completed, patients will have followup evaluations every 3 months, 6 months, and annually for 5 years. Evaluations will include blood samples and periodic bone marrow biopsies.
Severe aplastic anemia (SAA) is a life-threatening blood disease which can be effectively treated with immunosuppressive drug regimens or allogeneic stem cell transplantation. However, 20-40% of patients without transplant options do not respond to immunosuppressive therapies, and have persistent severe cytopenias, requiring regular platelet transfusions, which are expensive and inconvenient, and are a risk for further serious bleeding complications. Thrombopoietin (TPO) is the principal endogenous regulator of platelet production and also stimulates hematopoietic stem and progenitor cells. A small molecule oral TPO-agonist, eltrombopag has been shown to increase platelets in healthy subjects and in patients with immune thrombocytopenic purpura (ITP), and received FDA approval in 2008 for the treatment of thrombocytopenia in ITP. This Phase 2, non-randomized pilot study of eltrombopag in aplastic anemia patients with immunosuppressive therapy refractory thrombocytopenia will test the safety and potential efficacy of eltrombopag treatment patients with refractory thrombocytopenia following immunosuppression for aplastic anemia. Subjects will initiate study medication at an oral dose of 50 mg/day, which will be increased up to 150 mg/day as clinically indicated to the lowest dose that maintains a stable platelet count 20,000/(micro)L above baseline while maximizing tolerability. Response will be assessed at 3-4 months. Platelet response is defined as platelet count increases to 20,000/L above baseline at three months. or stable platelet counts with transfusion independence for a minimum of 8 weeks. Erythroid response for subjects with a pretreatment hemoglobin of less than 9 g/dL will be defined as an increase in hemoglobin by greater than or equal to 1.5g/dL without packed red blood cell (PRBC) transfusion support, or a reduction in the units of transfusions by an absolute number of at least 4 PRBC transfusions for eight consecutive weeks compared with the pretreatment transfusion number in the previous 8 weeks. Neutrophil response will be defined in those with a pretreatment absolute neutrophil count (ANC) of less than 0.5 times 10(9)/L as at least a 100 percent increase or an absolute increase greater than 0.5 times 10(9)/L. Subjects with response at 3-4 months may continue study medication (extended access) until they meet an off study criteria. The primary objective is to assess the safety and efficacy of the oral thrombopoietin receptor agonist (TPO-R agonist) eltrombopag in aplastic anemia patients with immunosuppressive-therapy refractory thrombocytopenia. Secondary objectives include the analysis of the incidence and severity of bleeding episodes, and the impact on quality of life.