29 Clinical Trials for Various Conditions
Fostamatinib may improve thrombocytopenia in myelofibrosis patients with severe thrombocytopenia (platelet \<50,000/microL) and allow them to initiate treatment with a JAK2 inhibitor, ruxolitinib. Additionally, fostamatinib monotherapy may also improve myelofibrosis related symptoms and splenomegaly.
Background: - Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens when people do not have enough normal platelets. Getting a transfusion of another person s platelets can help stop too much bleeding. But because these cells are from other people, the body may reject them,putting them at risk for serious bleeding complications. This conditions is called alloimmune platelet refractoriness . There are evidence that in many patients, platelet counts fail to increase after a platelet transfusion because the transfused platelets are destroyed by the body s defence soldier, called complement . Researchers want to see if a drug, that inhibits complement, can help increase platelet levels and reduce bleeding Objectives: - To see if eculizumab increases platelet levels more after a transfusion. To see if it reduces the chance of bleeding too much. Eligibility: - Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness. Design: * Participants will be screened with medical history, physical exam, and blood tests. * Participants will have the procedures listed below. They can have them while they are in the hospital. Or they can go to the outpatient clinic for them. Each visit may take up to 3 hours. * Participants will get a meningitis vaccine if needed. Then they will get the study drug as an infusion. * Participants will have a platelet transfusion. Their blood will be drawn every 24 hours until the platelet count is less than 10,000 per 1 microliter of blood. * They will take antibiotics for 14 days. * Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get more transfusions if needed.
This is an open-label study in which oprelvekin will be administered for the prevention of severe low blood platelet cell counts (cells in your blood that keep bleeding and clotting stable) in adults with cancer who are taking chemotherapy (anti-cancer drug) that has a side effect of blocking your bone marrow from making platelet cells. The purpose of this study is to learn more about the effects of the recommended dose of oprelvekin on the heart's electrical cycle.
A phase II trial of a reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for idiopathic severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT) utilizing population pharmacokinetic (popPK)-guided individual dosing of pre-transplant conditioning and differential dosing of low dose total body irradiation based on age, presence of myelodysplasia and/or clonal hematopoiesis.
Background: Severe aplastic anemia (SAA) is a rare and serious blood disorder. It causes the immune system to turn against bone marrow cells. Standard treatment for SSA is a combination of 3 drugs (Cyclosporine \[CsA\], Eltrombopag \[EPAG\], and horse anti-thymocyte globulin \[h-ATG\]). Researchers want to see if starting people at a lower dose of CsA with EPAG before giving them h-ATG is helpful. Objective: To learn if early initiation of oral therapy with CsA and EPAG is safe and effective in people who have SAA and have not been treated with a course of immunosuppressive therapy and EPAG. Eligibility: People ages 3 and older with SAA Design: Participants will be screened with: medical history physical exam electrocardiogram blood tests family history bone marrow biopsy current medicines. Participants may be screened remotely via telephone conference. Participants will take a lower oral dose of CsA and EPAG. They will take CsA twice a day for 6 months. They will take EPAG for 6 months. Those who cannot visit the NIH Clinical Center within 72 hours will start taking the drugs at home. They will have weekly telephone calls with NIH staff until they visit the Clinical Center. Participants may get h-ATG at the Clinical Center for 4 days. For this, they will have a central line placed. It is a plastic tube inserted into a neck, chest, or arm vein. Participants will repeat most screening tests throughout the study. Participants will have follow-up visits at the Clinical Center at 3 months, 6 months, and annually for 5 years after the start of the study....
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 aplastic anemia is a rare and serious blood disorder. It happens when the immune system starts to attack the bone marrow cells. This causes the bone marrow to stop making red blood cells, platelets, and white blood cells. Standard treatment for this disease is horse-ATG and cyclosporine, which suppress the immune system and stop it from attacking the bone marrow. However, this treatment does not work in all people. Some people still have poor blood cell counts even after treatment. * Eltrombopag is a drug designed to mimic a protein in the body called thrombopoietin. It helps the body to make more platelets. It may also cause the body to make more red and white blood cells. Studies have shown that eltrombopag may be useful when added to standard treatment for severe aplastic anemia. It may help improve poor blood cell counts. Objectives: - To test the safety and effectiveness of adding eltrombopag to standard immunosuppressive therapy for severe aplastic anemia. Eligibility: - Individuals at least 2 years of age who have severe aplastic anemia that has not yet been treated. Design: * Participants will be screened with a physical exam, medical history, and blood tests. Blood and urine samples will be collected. * Participants will start treatment with horse-ATG and cyclosporine. Treatment will be given according to the standard of care for the disease. * Cohort 1: After 14 days, participants will start taking eltrombopag. They will take eltrombopag for up to 6 months. * Cohort 2: After 14 days, participants will start taking eltrombopag. They will take eltrombopag for up to 3 months. * Cohort 3 and Extension Cohort: Participants will start taking eltrombopag on Day 1. They will take eltrombopag for up to 6 months. * Participants may receive other medications to prevent infections during treatment. * Treatment will be monitored with frequent blood tests. Participants will also fill out questionnaires about their symptoms and their quality of life.
The main purpose of this study is to compare how one 50 mg tablet of SB-497115 is broken down in the body by healthy subjects versus subjects with mild, moderate or severe kidney problems. The study is also being done to 1) check on how well the study drug is tolerated by healthy subjects versus those with liver problems and 2) to check if liver impairment affects how the study drug binds to protein in the blood.
The main purpose of this study is to compare how one 50mg tablet of SB-497115 is broken down in the body by healthy subjects versus subjects with mild, moderate or severe liver problems. The study is also being done to 1) check on how well the study drug is tolerated by healthy subjects versus those with liver problems and 2) to check if liver impairment affects how the study drug binds to protein in the blood.
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation offers the opportunity for cure in 70% of patients, but most patients are not suitable candidates for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a histocompatible donor. For these patients, comparable long term survival is attainable with immunosuppressive treatment with anti-thymocyte globulin (ATG) and cyclosporine (CsA). However, of those patients treated with horse ATG(h-ATG)/CsA, one quarter to one third will not respond, and about 50% of responders relapse. Auto-reactive T cells may be resistant to the effect of ATG/CsA (non-responders), while in others residual auto-reactive T cells expand post-treatment, leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). As long term survival is correlated to response rates and robustness of hematopoietic recovery, novel immunosuppressive regimens that can achieve hematologic response and decrease relapse rates are needed. This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint, as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution. Randomization is employed to obtain an equal distribution of subject to each arm; comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms (rabbit-ATG \[r-ATG\] versus standard h-ATG; alemtuzumab vs standard h-ATG). For long course CSA, comparison of primary end points will be to well established historic relapse rate of 38% at 2-3 years and a cumulative rate of clonal evolution of 15%.
Due to an overall and disease free survival of 85% to 100%, allogeneic blood or bone marrow stem cell transplantation using an HLA matched sibling donor is the therapy of choice for patients with severe aplastic anemia (SAA). Unfortunately, only about 25% of patients have such a donor. For patients with SAA lacking a matched sibling donor, immunosuppressive therapy is the current treatment of choice. Approximately 70% of these patients have a complete or partial response to immunosuppressive therapy, achieving transfusion independence and/or growth factor independence. For the approximately 30% of patients who do not respond to immunosuppressive therapy or experience recurrence, alternative donor (matched unrelated, partially matched family member) transplantation is a treatment option. However, graft rejection and graft-versus-host-disease (GVHD) are significant barriers to success, decreasing event-free survival to 30% to 50%. This study offers stem cell transplantation using a partially matched family member (haploidentical) donor to those patients with no available HLA-matched sibling or matched unrelated donor. In an attempt to reduce GVHD and regimen-related toxicity while maintaining adequate engraftment, we plan to infuse a highly purified stem cell graft. The Miltenyi Biotec CliniMACS CD3 depletion system will be used to derive a defined allogeneic graft highly enriched for CD34+ hematopoietic cells and depleted of CD3+ T-lymphocytes from G-CSF mobilized, donor-derived peripheral blood stem cells. Patients 21 years of age and younger with refractory cytopenias are also eligible for this protocol as there are no other potentially curative therapies currently available for these conditions. The primary objective of this study is to evaluate the safety of transplantation using a haploidentical donor product engineered to targeted cell counts using the investigational CliniMACS device for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can find this type of procedure is associated with a significantly higher treatment failure rate. Treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days after transplant.
This study will evaluate the safety and usefulness of a new immunosuppressive drug, alemtuzumab (Campath ), in patients with severe aplastic anemia (SAA). SAA is a rare and serious blood disorder in which the bone marrow stops making red blood cells, white blood cells and platelets. Alemtuzumab is a monoclonal antibody that attaches to and kills white blood cells called lymphocytes. In certain types of aplastic anemia, lymphocytes are responsible for the destruction of stem cells in the bone marrow, leading to a decrease in blood counts. Because alemtuzumab destroys lymphocytes, it may be effective in treating aplastic anemia. Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and is also helpful in other conditions that require immunosuppression, such as rheumatoid arthritis and immune cytopenias. Patients 2 years of age and older with severe aplastic anemia whose disease does not respond to immunosuppressive therapy or has recurred following immunosuppressive therapy may be eligible for this study. Participants undergo the following tests and procedures: * Pretreatment evaluation: Patients have a medical history, physical examination, blood tests, electrocardiogram (EKG), echocardiogram, 24-hour Holter monitor (continuous 24-hour monitoring of electrical activity of the heart), bone marrow biopsy (withdrawal through a needle of a small sample of bone marrow for analysis). * Placement of a central line, if needed: An intravenous line (tube) is placed into a major vein in the patient's chest. It can stay in the body for the entire treatment period and be used to give chemotherapy or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. * Alemtuzumab therapy: Patients are admitted to the NIH Clinical Center for the first few injections for close monitoring of side effects. After receiving an initial small test dose, patients begin the first of ten daily injections under the skin, each lasting about 2 hours. Once patients tolerate the infusions with minimal or no side effects, they may be given the remaining infusions on an outpatient basis. Patients who relapse after their initial response to alemtuzumab are given cyclosporine to see if this drug will boost their immune response. * Patients receive transfusions, growth factors, and antibiotic therapy, as needed. * Infection therapy: Patients are given aerosolized pentamidine to protect against lung infections and valacyclovir to protect against herpes infections. * A blood test is done and vital signs are measured every day while patients receive alemtuzumab. * Patients have an echocardiogram and 24-hour Holter monitor after the last dose of alemtuzumab. * Blood tests are done weekly for the first 3 months after alemtuzumab administration, then every other week until 6 months. Patients return to the NIH for follow-up visits 1 month, 3 months, 6 months, and yearly for 5 years after the last dose of alemtuzumab for the following tests and evaluations: * Blood test * Repeat echocardiogram at 3-month visit * Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab, then as clinically indicated for 5 years.
Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients may benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggest that patients with poor blood count responses to a single course of ATG, even when transfusion-independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement. The management of such cases is uncertain. This study will enroll patients who are either refractory to h-ATG (continued severe pancytopenia) or who have only modest improvement in blood counts (weak hematologic responders) to receive a further immunosuppressive therapy, delivered either as rabbit ATG (Thymoglobulin, r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H ). Primary endpoint will be response rate at 3 months defined as no longer meeting criteria for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 3 months, survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia and acute leukemia will be the secondary endpoints.
RATIONALE: Studying samples of blood in the laboratory from patients receiving temozolomide may help doctors learn how temozolomide works in the body. It may also help doctors learn more about how a patient's genes may affect the risk of developing thrombocytopenia. PURPOSE: This clinical trial is studying the pharmacokinetics in patients with newly diagnosed high-grade glioma receiving temozolomide and radiation therapy.
Open-label randomized controlled trial to test the effectiveness of whole blood transfusion for improving survival in children with severe malaria complicated by thrombocytopenia.
RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with methotrexate and methylprednisolone may stop this from happening. PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and busulfan works when given before donor stem cell transplant in treating young patients with hematologic disorders.
OBJECTIVES: I. Ascertain whether stem cell transplantation (SCT) is an effective method by which missing or dysfunctional enzymes can be replaced in patients with various inborn errors of metabolism. II. Determine whether clinical manifestations of the specific disease may be arrested or reversed by this treatment.
Children, adolescents, and young adults with malignant and non-malignant conditionsundergoing an allogeneic stem cell transplantation (AlloSCT) will have the stem cells selected utilizing α/β CD3+/CD19+ cell depletion. All other treatment is standard of care.
In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) to determine the minimum effective dose required for reliable engraftment for subjects undergoing hematopoietic stem cell transplantation for non-malignant disease.
This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells.
The purpose of this study is to collect and store samples and health information for current and future research to learn more about the causes and treatment of blood diseases. This is not a therapeutic or diagnostic protocol for clinical purposes. Blood, bone marrow, hair follicles, nail clippings, urine, saliva and buccal swabs, left over tissue, as well as health information will be used to study and learn about blood diseases by using genetic and/or genomic research. In general, genetic research studies specific genes of an individual; genomic research studies the complete genetic makeup of an individual. It is not known why many people have blood diseases, because not all genes causing these diseases have been found. It is also not known why some people with the same disease are sicker than others, but this may be related to their genes. By studying the genomes in individuals with blood diseases and their family members, the investigators hope to learn more about how diseases develop and respond to treatment which may provide new and better ways to diagnose and treat blood diseases. Primary Objective: * Establish a repository of DNA and cryopreserved blood cells with linked clinical information from individuals with non-malignant blood diseases and biologically-related family members, in conjunction with the existing St. Jude biorepository, to conduct genomic and functional studies to facilitate secondary objectives. Secondary Objectives: * Utilize next generation genomic sequencing technologies to Identify novel genetic alternations that associate with disease status in individuals with unexplained non-malignant blood diseases. * Use genomic approaches to identify modifier genes in individuals with defined monogenic non-malignant blood diseases. * Use genomic approaches to identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease. * Use single cell genomics, transcriptomics, proteomics and metabolomics to investigate biomarkers for disease progression, sickle cell disease (SCD) pain events and the long-term cellular and molecular effects of hydroxyurea therapy. * Using longitudinal assessment of clinical and genetic, study the long-term outcomes and evolving genetic changes in non-malignant blood diseases. Exploratory Objectives * Determine whether analysis of select patient-derived bone marrow hematopoietic progenitor/stem (HSPC) cells or induced pluripotent stem (iPS) cells can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms. * Determine whether analysis of circulating mature blood cells and their progenitors from selected patients with suspected or proven genetic hematological disorders can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.
This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.
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.
This phase II trial studies how well giving fludarabine phosphate, melphalan, and low-dose total-body irradiation (TBI) followed by donor peripheral blood stem cell transplant (PBSCT) works in treating patients with hematologic malignancies. Giving chemotherapy drugs such as fludarabine phosphate and melphalan, and low-dose TBI before a donor PBSCT helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune response against the body's normal cells. Giving tacrolimus, mycophenolate mofetil (MMF), and methotrexate after transplant may stop this from happening
This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.
The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).
The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.