22 Clinical Trials for Various Conditions
Background: Hypereosinophilic syndrome (HES) is a blood disorder that causes high levels of white blood cells called eosinophils. HES can damage the lungs and airways, intestines, skin, and other organs. The current primary treatment for HES can cause serious side effects. Secondary treatments do not work in all people. Objective: To test an approved drug (dupilumab), combined with other drugs, in people with HES. Eligibility: People aged 18 years and older who take drugs (mepolizumab, reslizumab, or benralizumab) to treat HES. Design: Participants will have up to 6 clinic visits and 7 remote visits in up to 48 weeks. Participants will be screened. They will have blood and urine tests. They will have a test of their heart function. They will take surveys about how HES affects their daily life. Some participants may have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle. Participants will have other tests specific to their symptoms. For example, those with symptoms affecting their lungs will have breathing tests. Others may have tests that target symptoms in their sinuses, gastrointestinal tract, or skin. Dupilumab is injected under the skin once every 1 or 2 weeks. Dose and timing will vary among participants. They will be taught how to inject themselves at home between clinic visits. They will take dupilumab plus their current medications for 24 weeks. If the drug is helping them, they will continue taking it for another 24 weeks. Participants will have a final visit 12 weeks after their last dose.
The purpose of this study is to build the knowledge base on clinical characteristics, clinical management, and treatment outcomes of HES.
This is a 52-week, randomized, placebo-controlled, double-blind, parallel group, multicenter study of depemokimab in adults with uncontrolled HES receiving standard of care (SoC) therapy. The study will recruit patients with a confirmed diagnosis of HES and who are on stable HES therapy for at least 4 weeks prior to randomization (Visit 2). Eligible participants must have uncontrolled HES with a history of repeated flare (≥2 flares in the previous 12 months) and blood eosinophil count of ≥1,000 cells/ microliter (μL) during Screening. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in therapy. Participants who meet the inclusion and exclusion criteria will be randomized in a 2:1 ratio to receive either depemokimab or placebo while continuing their SoC HES therapy.
The purpose of this study is to investigate the efficacy and safety of mepolizumab in children and adolescents with hypereosinophilic syndrome (HES) who are receiving standard of care (SoC) therapy.
This is a multicentre, randomised, double-blind (DB), parallel-group, placebo-controlled, 24-week Phase III study to compare the efficacy and safety of benralizumab versus placebo administered by SC injection Q4W in patients with hypereosinophilic syndrome (HES). This study comprises 2 distinct periods (together defined as the 'main study'): A 24-week, DB treatment period, during which patients will be randomised to receive either benralizumab or placebo, in addition to their prior stable HES background therapy, and an open-label extension (OLE) period, during which all patients will receive benralizumab. The primary database lock (DBL) will occur when approximately 38 patients have had their first HES worsening/flare event during the DB treatment period and all randomised patients have had the opportunity to be followed up for the 24-week DB treatment period. A patient must complete the 24-week DB treatment period on investigational product (IP) to be eligible to enter the OLE treatment period. The final DBL will occur after the last patient completes the OLE.
This phase II trial studies how well ruxolitinib works in treating patients with hypereosinophilic syndrome or primary eosinophilic disorders.
This is an open-label extension study to Study 200622.In this study subjects from Study 200622 will be continued on 4-weekly dosing with open-label mepolizumab 300 milligram (mg) subcutaneously (SC) for an additional 20 Weeks after completing the 32 Week study assessments post-randomization, while they continue with their background HES therapy per standard of care (SoC). Subjects from study 200622 will participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization. Data from this study (205203) and 200622 will be combined to provide up to 52-Week exposure data to further characterize the long-term safety profile of mepolizumab and provide additional data on the clinical benefit in HES subjects beyond 32 Weeks. The duration of the study participation will be 20 Weeks for subjects who continue with mepolizumab treatment via MHE104317/MHE112562 after this open-label extension study; and 28 Weeks for subjects who do not continue with MHE104317/MHE112562.
Mepolizumab is a humanized monoclonal antibody. In conditions where eosinophilia is considered to play an important part in the pathology, including eosinophilic asthma, HES, and eosinophilic granulomatosis with polyangiitis, a consistent reduction in blood eosinophil counts is observed in association with mepolizumab administration, with concomitant clinical improvement. This is a 32-week treatment period, randomized, double-blind, placebo-controlled, parallel group, multicentre study of mepolizumab in adolescent and adult subjects with severe HES receiving standard of care (SoC) therapy. This study will demonstrate the efficacy of mepolizumab compared with placebo based on maintenance of control of HES symptoms during the treatment period. The study will comprise of a screening period of up to approximately 4 weeks followed by a 32-Week study treatment period (subjects will be randomized 1:1 to placebo or mepolizumab) and up to 8-week additional follow-up period (12 weeks after the last dose of study treatment).
Background: - Eosinophils are white blood cells that help fight infections. High eosinophil levels can damage people s organs, causing hypereosinophilic syndrome (HES). Researchers want to study if the drug benralizumab can help people with HES. Objective: - To test if benralizumab can safely decrease eosinophils in people with HES. Eligibility: - Adults age 18-65 who have been on stable HES therapy for at least 1 month but still have symptoms and high eosinophil levels. Design: * Participants will be screened with medical history, physical exam, and urine and blood tests. They will take simple heart and lung tests. * Participants will also have a bone marrow biopsy. A numbing medicine is injected into the outer covering of the bone. Then a needle is inserted into the bone. A fast suction movement takes bone marrow cells. * Phase 1: Participants will randomly receive either the study drug or placebo as an injection. * They will have daily visits for the next 3 days, then 4 weekly visits, and then 4 biweekly visits. Each time, they will have medical history, physical exam, blood tests, and a check of side effects. * They will receive another dose of the study drug or placebo at 1 month and 2 months after the first injection. * Phase 2 repeats the Phase 1 schedule. All participants will receive the study drug. * At 1 visit, participants will also receive a vaccine. At 4 visits, they will repeat the heart and lung tests. They will also have one other bone marrow biopsy. * After week 24, participants will receive the study drug either 6 times over 6 months or twice over 6 months.
Background: - Eosinophils are white blood cells that fight infections. In people with hypereosinophilic syndrome (HES), eosinophil levels are too high and can damage their organs. HES is usually treated with steroids, but steroids can cause side effects and stop working over time. Researchers want to see if a drug called dexpramipexole, being developed by Knopp Pharmaceuticals, can help people with HES to reduce their steroid dose. Objective: - To test whether dexpramipexole can reduce the steroid dose needed to control eosinophilia and HES symptoms. Eligibility: - Adults 18 and older with HES who respond to steroids, but need more than 10 mg daily to control eosinophilia and symptoms. Design: * The study will last 9 months with 6 visits to NIH. * Participants will be screened with medical history, physical exam, and urine and blood samples. * Participants steroids will be tapered to the lowest effective dose. During this time, blood will be drawn weekly. Participants will take this dose for 2 weeks before starting the study drug. * Participants will take the study drug twice daily by mouth for 12 weeks along with steroids. The steroid dose will not be decreased during this time and participants will be seen monthly for a medical history, physical examination and blood work. * Just before and 12 weeks after starting the study drug, the following tests will be performed: * medical history and physical exam * blood and urine tests * lung function tests * electrocardiogram (measures heart electrical activity) * echocardiogram (takes pictures of the heart using sound waves) * bone marrow biopsy (a needle inserted into the hip bone that removes bone marrow cells for study) * After 12 weeks, the participants steroid dose will be tapered again to the lowest effective dose while on study drug. * Two weeks after the lowest effective dose is reached, participants will return for a medical history, physical examination, blood work, lung and heart tests. * Participants who respond to the study drug may be able to continue to receive the drug on a planned separate study. * Four weeks after stopping the study drug, participants will have medical history, physical exam, and blood tests.
Background: - Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart, nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage. Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although most people respond to prednisone, some people develop side effects from it, or do not respond very well to treatment. Better ways of determining the dose to give could help to decide on the best therapy for HES. Objectives: * To determine whether a single-dose of prednisone can be used to predict which people with hypereosinophilia respond to treatment. * To study lack of response to steroid treatment in people with HES. Eligibility: Inclusion criteria: * Individuals with hypereosinophilic syndrome with high eosinophil counts. * Individuals who are willing to have blood drawn before and after getting steroids. Exclusion criteria: * Individuals who are on more than 10mg of prednisone (or similar drug) * Individuals with hypereosinophilic syndrome who are on other medications that could interfere with the study * Women who are pregnant or breast-feeding * Individuals who have a known gene mutation associated with chronic eosinophilic leukemia * Children less than 18 years old who weigh less than 48kg or 106lb Design: * Participants will have a screening visit with a physical exam and medical history. Blood and urine samples will be collected. * Participants will have a single dose of the steroid prednisone by mouth in the morning. Blood samples will be collected 2, 4, 24 hours after this dose. * On the day after the steroid dose, participants will provide another blood sample in the morning. * Participants will start to take prednisone daily when they return home. Blood samples will be collected weekly at the participant s doctor s office. The dose of prednisone will be lowered depending on the weekly eosinophil count. We will try to get each person on the lowest dose of prednisone possible that will control the disorder. Participants who do not respond or have severe side effects will be taken off prednisone. Other treatments will be considered for people who do not respond to steroids. The goal is to evaluate the response to prednisone. Our research will try to figure out why some people do not respond to steroids. Most people will complete the study within 6 to 16 weeks, depending on their response to prednisone.
Primary Objectives: 1. To determine the response rate, progression-free survival (PFS) and overall survival of patients who receive 2-CdA + Ara-C. 2. To examine if there is any clonality in the cytokine expression of helper T cells or cytokine receptor expression of eosinophils. 3. To determine the effect of 2-CdA on accumulation of Ara-C triphosphate in eosinophils.
Toxicity of anti-IL-5
The purpose of the trial is to determine the safety and efficacy of Gleevec" in idiopathic hypereosinophilic syndrome (HES) and to characterize the molecular basis for the therapeutic benefit of Gleevec" in HES.
This is an open label study of mepolizumab 750 mg intravenous in those subjects who participated in study 100185 to evaluate the long term safety and efficacy of mepolizumab in subjects with hypereosinophilic syndrome. The study will also evaluate the optimal dosing frequency for clinical use, the effects on corticosteroid reduction, and decrease of signs and symptoms of Hypereosinophilic Syndrome.
Hypereosinophilic syndrome (HES) is a rare disease with broad clinical signs and symptoms which is diagnosed based on a persistent blood eosinophil count of greater than 1500 cells, various end-organ damages (including skin, heart, lung, nervous system and digestive system etc.), and with exclusion of known secondary causes of hypereosinophilia. HES has a high morbidity/mortality rate. The major treatment of HES has been systemic corticosteroid and other chemotherapeutic drugs (for example, hydroxyurea and interferon) with the intention to lower eosinophil counts and therefore to slow down the progression of disease. Even though corticosteroid and other therapies can effectively reduce eosinophilia in some patients, some may eventually become nonresponsive and intolerable to the amount of side effects of the long-term therapy with these medications. Mepolizumab is a humanized monoclonal antibody that binds specifically to human interleukin 5 (hIL-5) and inhibits its activity. Previous human experience has shown it has been effective in reducing blood eosinophilia in atopic and HES patients and has alleviated some HES clinical signs and symptoms. This study intends to further evaluate the corticosteroid-sparing and clinical benefit of mepolizumab in HES.
The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients with the myeloid form of hypereosinophilic syndrome (HES). Patients with the hypereosinophilic syndrome who meet a set of criteria designed to select patients with the myeloid form of the disease, as well as patients without myeloid disease who are refractory to standard therapy for HES, will be admitted on this protocol. A thorough clinical evaluation will be performed with emphasis on potential sequelae of eosinophil-mediated tissue damage. A baseline bone marrow will be obtained to exclude leukemia or lymphoma and to assess the degree and nature of eosinophilopoiesis. Bone marrow, blood cells and/or serum will also be collected to test for the presence of a recently described mutation that is associated with imatinib-responsiveness in HES, and to provide reagents (such as DNA, RNA, and specific antibodies) and for use in the laboratory to address issues related to the mechanism of action of imatinib mesylate in HES. Imatinib mesylate will be initiated at a dose of 400 mg daily, the FDA-approved dose for the treatment of chronic myelogenous leukemia. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100mg daily and then discontinued. In order to minimize bone marrow suppression, other myelosuppressive agents will be tapered and discontinued during the first week of therapy with imatinib mesylate. Complete blood counts will be performed weekly for the first month and biweekly thereafter. Clinical assessments will be performed every three months to assess progression of end organ damage. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100 mg daily and then discontinued. In the event of clinical, hematologic or molecular relapse during the taper, the imatinib dose will be increased to a maximum of 600 mg daily to achieve a second remission. Laboratory monitoring will be performed as above except for molecular monitoring which will be monitored monthly if drug is discontinued or molecular relapse occurs. Once a stable dosing regimen is achieved for greater than or equal to 6 months in subjects who have undergone dose descalation or greater than or equal to 2 years in subjects receiving 300-400 mg of imatinib daily who did not qualify for dose de-escalation, the frequency of NIH visits and end organ assessments will be decreased to 6 months, with molecular monitoring every 3 months and monthly routine laboratory assessments. ...
This study will examine the safety and effectiveness of a single dose of anti-interleukin-5 antibody (SCH 55700) in reducing the number of eosinophils (a type of white blood cell) in patients with hypereosinophilic syndrome. Patients with this disease have too many eosinophils in the blood and in body tissues, which cause damage to the affected organs-most commonly the heart, nerves and skin. SCH 55700 is an antibody to interleukin 5-a hormone-like substance produced by white blood cells that plays a significant role in eosinophilia. SCH 55700 has lowered eosinophilia blood counts in patients with asthma and reduced the number of these cells in tissues of animals with asthma. Patients with hypereosinophilic syndrome 18 years of age and older who have not responded to standard therapy with steroids, interferon and hydroxyurea or cannot take these drugs may be eligible for this study. Candidates will be screened with a medical history, physical examination, eye examination, and blood tests. Depending on the patient's symptoms, other diagnostic tests may be done, including studies of the eyes, lungs, skin, nerves or heart. Skin biopsy and bronchoalveolar lavage may be included in the diagnostic evaluation. For the skin biopsy, a small area about 1/3 inch in diameter is numbed and a small core of skin is surgically removed for study under the microscope. Bronchoalveolar lavage involves inserting a catheter (flexible tube) into the lungs to instill saline (salt water) and obtain a tissue sample. This test will be done only if clinically necessary. Those enrolled in the study will be admitted to the NIH Clinical Center for a single dose of SCH 55700, injected into an arm vein. They will be monitored in the hospital for at least 72 hours for changes in eosinophil count and side effects of the injection. After discharge, laboratory tests will be done weekly for the first month, either at the Clinical Center or by the patient's local physician. Follow-up visits will then be scheduled monthly for 1 year or until the patient's eosinophil count returns to pre-treatment levels for 2 consecutive months. Follow-up visits will include a history, physical examination and blood tests, including studies on how immune cells and other substances in the blood activate or stimulate eosinophilia. A chest X-ray, electrocardiogram and pulmonary function tests will be done at 1, 3, 6 and 12 months to evaluate organ damage. Other tests may be done if medically indicated. Bone marrow biopsy and aspiration will be done before receiving SCH 55700 and one month after the injection to evaluate the effects of SCH 55700 on eosinophil production in the bone marrow. For this test, an area of skin and bone is numbed and a very sharp needle is used to withdraw a sample of the bone marrow. Leukapheresis will also be done before and 1 month after SCH 55700 treatment to obtain cells for studying the effect of SCH 55700 on eosinophil activation, function and survival. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm.
The goal of this clinical research study is to learn if dasatinib can help to control myeloproliferative disorders. The safety and tolerability of dasatinib will also be studied.
The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions: Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1) Group A - Imatinib failure only (arms 2, 3 and 4) * imatinib-resistant or intolerant CML - Chronic Phase (CP) * imatinib-resistant or intolerant CML - Accelerated Phase (AP) * imatinib-resistant or intolerant CML - Blast Crisis (BC) Group B - Imatinib and other TKI failure (arms 2, 3 and 4) * imatinib-resistant or intolerant CML - Chronic Phase (CP) * imatinib-resistant or intolerant CML - Accelerated Phase (AP) * imatinib-resistant or intolerant CML - Blast Crisis (BC) Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5) Systemic mastocytosis (Sm) (arm 6)
Eosinophils are a type of white blood cell. Elevated eosinophil levels can damage the heart, nerves, and other organs, in the syndrome known as hypereosinophilic syndrome (HES). Some individuals have a hereditary form of HES known as familial eosinophilia (FE). More research on the causation and mechanisms of HES is needed in order to design more effective and less toxic therapies. This study will investigate FE and its genetic causes, damage mechanisms, and disease markers (such as blood test abnormalities). It will enroll approximately 50 individuals (both adults and children) from a previously studied family with FE. This is a long-term study of indefinite duration. Participants will undergo yearly clinical examinations including medical history, physical examination, bloodwork, EKG, echocardiogram, and pulmonary function tests, with additional or more frequent examinations and tests as required. In addition, participants will donate blood and tissue for research purposes. Both adult and child participants will donate blood. At the initial evaluation, adult participants will donate bone marrow. During the study, some adult participants will also undergo a limited number of leukaopheresis sessions, in which blood is donated from one arm, the blood is separated into red blood cells and other components, and the red blood cells are returned into the donor's other arm. ...
The goal of this clinical research study is to see if Gleevec, known as imatinib mesylate (STI571), can improve the disease condition in patients with hypereosinophilic syndrome, polycythemia vera, atypical CML or CMML with PDGF-R fusion genes, or mastocytosis.