Active clinical trials for "Anemia, Aplastic"

This is a single-dose, open-label, phase I clinical study evaluating the PK of hetrombopag in subjects with mild hepatic impairment (Child-Pugh Class A), subjects with moderate hepatic impairment (Child-Pugh Class B), as well as age-, weight-, and gender-matched subjects with normal hepatic function.

This was a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/microliter who were refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST. Eltrombopag was expected to improve trilineage blood cells and decrease transfusion frequency based on the result from the previous study in patients with severe AA. This study used the hematologic response rate, defined as the proportion of subjects showing improvement in at least one of the three blood cell lineages or a decrease in blood transfusion volume, as the primary endpoint. A total of 36 subjects were screened and 21 were enrolled in the study. Treatment with eltrombopag started at 25 milligram (mg)/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day. Response assessment was performed at 3 months after starting the study treatment (Week 13). Subjects in whom the treatment was assessed as effective continued with the study treatment. Subjects in whom the treatment was assessed as effective (when meeting any of the response criteria) at 6 months after starting the study treatment (Week 26) might enter the extension phase and continue the treatment with eltrombopag. The primary endpoint was the hematologic response rate at Week26.

The primary hypothesis of this research study is that patients in remission undergoing myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS) rate at 1 year that is the same or better than the historical DFS of patients with similar diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS rate of 50% or better at 1 year would meet the criterion for an effective alternative therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach over T-replete matched sibling HSCT.

Background: - Eltrombopag is a drug being tested for treating severe aplastic anemia. It can help improve blood counts in these patients. However, researchers do not know how long the drug can and should be taken for this type of anemia. Objectives: - To look at whether 6 months of treatment with eltrombopag can improve patient s blood counts. Eligibility: - Individuals at least 2 years of age who are taking eltrombopag for severe aplastic anemia. Design: Participants will take eltrombopag by mouth once a day for 6 months. Blood samples will be collected every 2 weeks for the first 6 months. Bone marrow samples will be collected at 3 and 6 months. These samples will look at the effects of the study drug on the marrow. Participants will continue to take the study drug for as long as it is effective and if the side effects are not severe.

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.

Allogeneic stem cell transplantation may provide long-term remissions for some patients with hematological malignancies. However, allogeneic transplantation is associated with a significant risk of potentially life threatening complications due to the effects of chemotherapy and radiation on the body and the risks of serious infection. In addition, patients may develop a condition called Graft versus host disease that arises from an inflammatory reaction of the donor cells against the recipient's normal tissues. The risk of graft versus host disease is somewhat increased in patients who are receiving a transplant from an unrelated donor. One approach to reduce the toxicity of allogeneic transplantation is a strategy call nonmyeloablative or "mini" transplants. In this approach, patients receive a lower dose of chemotherapy in an effort to limit treatment related side effects. Patients undergoing this kind of transplant remain at risk for graft versus host disease particularly if they receive a transplant from an unrelated donor. The purpose of this research study is to examine the ability of a drug called CAMPATH-1H to reduce the risk of graft versus host disease and make transplantation safer. CAMPATH-1H binds to and eliminates cells in the system such as T cells that can cause graft versus host disease (GvHD). As a result, earlier studies have shown that patients who receive CAMPATH-1H with an allogeneic transplant have a lower risk of GvHD. In the present study, we will examine the impact of treatment with CAMPATH-1H as part of an allogeneic transplant on the development of GvHD and infection. In addition, we will study the effects of CAMPATH-1H on the immune system by testing blood samples in the laboratory.

Transplantation with stem cells is a standard therapy in many centers around the world. Previous experience with stem cell transplantation therapy for leukemias, lymphomas, other cancers, aplastic anemia and other non-malignant diseases, has led to prolonged disease-free survival or cure for some patients. However, the high doses of pre-transplant radiation and chemotherapy drugs used, and the type of drugs used, often cause many side effects that are intolerable for some patients. Slow recovery of blood counts is a frequent complication of high dose pre-transplant regimens, resulting in a longer period of risk for bleeding and infection plus a longer time in the hospital. Recent studies have shown that using lower doses of radiation and chemotherapy (ones that do not completely kill all of the patient's bone marrow cells) before blood or bone marrow transplant, may be a better treatment for high risk patients, such as those with Dyskeratosis Congenita (DC) or Severe Aplastic Anemia(SAA). These low dose transplants may result in shorter periods of low blood counts, and blood counts that do not go as low as with traditional pre-transplant radiation and chemotherapy. Furthermore, in patients with Dyskeratosis Congenita or SAA, the stem cell transplant will replace the blood forming cells with healthy cells. It has recently been shown that healthy marrow can take and grow after transplantation which uses doses of chemotherapy and radiation that are much lower than that given to patients with leukemia. While high doses of chemotherapy and radiation may be necessary to get rid of leukemia, this may not be important to patients with Dyskeratosis Congenita or SAA. The purpose of this research is to see if this lower dose chemotherapy and radiation regimen followed by transplant is a safe and effective treatment for patients with Dyskeratosis Congenita or SAA.

Objectives: To evaluate disease free survival after Campath 1H-based in vivo T-cell depletion and non-myelo-ablative ablative stem cell transplantation in patients with hematologic malignancies. To evaluate the incidence and severity of acute and chronic GVHD after Campath 1H-based in vivo T-cell depletion, in patients with hematologic malignancies undergoing non-myelo-ablative stem cell transplantation. To evaluate engraftment and chimerism after Campath 1H-based in vivo T-cell depletion and non-myelo-ablative ablative stem cell transplantation in patients with hematologic malignancies.

The purpose of this study is to transplant haploidentical related peripheral blood stem cells (PBSCs) that come from a relative such as a parent, sibling, a child or other relative who has a half-matched tissue type with the recipient (rather than being completely matched) following administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab.