Treatment Trials

65 Clinical Trials for Various Conditions

Focus your search

Eculizumab Pharmacokinetics/Pharmacodynamics Study in Pediatric/Adolescent Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

The primary objective of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameter estimates of eculizumab to confirm the dose regimens for pediatric and adolescent participants with PNH.

Conditions

Hemoglobinuria, Paroxysmal

The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.

Conditions

Hemoglobinuria, Paroxysmal

The Paroxysmal Nocturnal Hemoglobinuria Early Access Treatment Protocol
Description

The primary objective is to provide access to eculizumab for PNH patient pending commercial availability.

Conditions

Hemoglobinuria, Paroxysmal

Eculizumab to Treat Paroxysmal Nocturnal Hemoglobinuria
Description

This study will evaluate the safety and effectiveness of the experimental drug eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a disorder that can cause premature destruction of red blood cells. PNH may result in anemia requiring blood transfusions. Patients may be at high risk of life-threatening blood clots in their veins and may have urine discoloration, stomach pain, difficulty swallowing, tiredness, and poor quality of life. Men may have problems getting or maintaining an erection. Eculizumab is a monoclonal antibody that may improve the survival of red blood cells in patients with PNH. Patients 18 years of age and older who have been diagnosed with PNH for more than 6 months, who have active disease, and who require blood transfusions may be eligible for this study. Each candidate is screened with a physical examination, electrocardiogram, blood and urine tests, and a questionnaire for information on how PNH affects the patient physically, socially, emotionally, and functionally. Participants receive infusions of eculizumab through a needle in a vein once a week for five doses and then every two weeks for another 24 doses. All patients are vaccinated against Neisseria meningitides, a bacteria that can cause symptoms, possibly including life-threatening meningitis, in susceptible people, including people who take eculizumab. At every treatment visit, patients update their health status, transfusion record, and medication use; review their laboratory results from the preceding visit; have vital signs measured; and provide a blood sample for laboratory tests. At selected visits, they also provide a urine sample, have a repeat electrocardiogram, and complete a questionnaire. At the final treatment visit, participants have a complete physical examination, in addition to the routine procedures.

Conditions

Paroxysmal Hemoglobinuria, Nocturnal

Study Using Eculizumab in Transfusion Dependent Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
Description

The primary objective is to evaluate the safety and efficacy of eculizumab in transfusion dependent patients with hemolytic PNH.

Conditions

Hemoglobinuria, Paroxysmal

Extension Study of Eculizumab in Patients With Transfusion Dependent Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

The purpose of this study is to evaluate the long-term safety of eculizumab in patients with transfusion dependent hemolytic PNH.

Conditions

Paroxysmal Hemoglobinuria, Nocturnal

Study of Safety in Hemolytic Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Treated With Eculizumab
Description

The primary objective is to evaluate the safety of eculizumab in patients with transfusion-dependent hemolytic PNH

Conditions

Hemoglobinuria, Paroxysmal

Eculizumab to Treat Paroxysmal Nocturnal Hemoglobinuria
Description

This study will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Patients may be at high risk of blood clots and may develop bone marrow failure or aplastic anemia, with low white blood cell and platelet counts. Eculizumab is a monoclonal antibody that may help improve the survival of red blood cells. Patients 18 years of age and older with PNH who require blood transfusions for anemia and have received at least four transfusions in the 12 months preceding evaluation for this study may be eligible to enroll. Candidates are screened with a medical history, physical examination, and check of vital signs. Participants have an electrocardiogram (EKG) and blood and urine tests, and are vaccinated against Neisseria meningitides, a common bacteria that can cause a disabling or fatal type of meningitis. They then enter an observation phase of the study, with monthly visits during which they complete a questionnaire; update their health status, transfusion record, and medication use; have their vital signs checked and PNH symptoms evaluated; have blood and urine tests; and receive a transfusion, if necessary. These visits continue for up to 3 months until patients receive a "qualifying" transfusion; that is, a transfusion given as a consequence of a certain hemoglobin level with symptoms or a different level without symptoms. Patients are then randomly assigned to receive either eculizumab or a placebo (salt solution with no active ingredient). Both study medications are given intravenously (through a vein) over 30 minutes once a week for five doses and then once every 2 weeks for another 11 doses. At each treatment visit (study weeks 0-24), patients update their health status, transfusion records, and medication use; have their vital signs checked; and provide a blood sample. At various visits, they also complete a questionnaire, provide a urine sample and have an EKG. At the last treatment visit (week 26 or the final visit for patients who end their participation before visit 18) patients have a complete physical examination in addition to the procedures listed above.

Conditions

Hemoglobinuria, Paroxysmal

Transfer of GPI-Linked Proteins to Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria
Description

This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion. Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study. Participants will come to the NIH Clinical Center for the following procedures: * Interview about the severity of their anemia-related symptoms * Blood test * Blood transfusion, if required. Patients will be transfused with compatible group O blood. The donor blood will be washed (rinsed with a salt solution) until it is 99% free of donor plasma. Group O blood is given instead of group A1 in order to be able to distinguish the patient's cells from the transfused cells. Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail. If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.

Conditions

Paroxysmal Hemoglobinuria

A Study of Pegcetacoplan in Pediatric Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

The purpose of this study is to evaluate the safety, effectiveness, and biological activity (how the investigational medication is processed by the body) of pegcetacoplan in 12-17 year-olds (adolescents) who have paroxysmal nocturnal hemoglobinuria (PNH).

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH), Paroxysmal Hemoglobinuria

Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States
Description

The purpose of this study is to look at whether the combination of lower-dose chemotherapy with two chemotherapy (anti-cancer) drugs, called busulfan and melphalan, and an antibody medication called alemtuzumab (Campath®), can prevent rejection of donor blood stem cells so that those cells take hold and build a healthy new blood cell factory after transplant. The study will also look at the safety of the combination of drugs and of the transplant of peripheral blood stem cells from a healthy relative or an unrelated donor.

Conditions

Hematologic Neoplasms, Multiple Myeloma, Anemia, Aplastic, Hemoglobinuria, Paroxysmal, Myelofibrosis

Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer
Description

The purpose of this study is to compare the effects (good and bad) of the medication basiliximab in combination with cyclosporine (investigational therapy) for the prevention of a complication of bone marrow transplantation known as graft-versus-host disease (GVHD). GVHD is a complication in which the cells of the transplanted bone marrow react against organs and tissues.

Conditions

Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukemia, Myelodysplasia, Non-Hodgkin's Lymphoma, Hodgkin's Disease, Multiple Myeloma, Myelofibrosis, Anemia, Aplastic, Hemoglobinuria, Paroxysmal

Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors
Description

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.

Conditions

Hematologic Neoplasms, Anemia, Aplastic, Hemoglobinuria, Paroxysmal, Multiple Myeloma

Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies
Description

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

Conditions

Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia (JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Hodgkin Lymphoma, Lymphoma, Non-Hodgkin (NHL), Myelodysplastic Syndrome (MDS)

Identifying Characteristics of Bone Marrow Failure Syndromes
Description

Bone marrow failure syndromes (BMFS) are rare disorders characterized by dysfunctional hematopoietic stem cells, which give rise to all red and white blood cells. The deficiency of blood cells, or cytopenia, caused by this malfunction leads to an assortment of diseases and disorders, all of which are characterized as BMFS. Because these diseases are rare, conducting research on them is difficult, and standards of treatment for most BMFS have yet to be developed. This study will collect clinical and laboratory data from people with BMFS to identify the characteristics and biological markers associated with these diseases over time. This information will assist doctors and researchers to develop better therapies and diagnostic tests that will help improve the management of BMFS and cytopenias.

Conditions

Bone Marrow Failure Syndromes, Anemia, Aplastic, Myelodysplastic Syndromes, Hemoglobinuria, Paroxysmal, Red-Cell Aplasia, Pure, Purpura, Thrombocytopenic, Leukemia, Lymphocytic

Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
Description

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD) and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. This research project will investigate the use of particular pre-transplant conditioning regimen (chemotherapy, antibodies and total body irradiation) followed by a stem cell infusion from a "mismatched" family member donor. Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device. The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment, as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment. Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor.

Conditions

Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia(JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Lymphoma, Non-Hodgkin (NHL), Myelodysplastic Syndrome (MDS)

Stem Cell Transplantation for Patients With Hematologic Malignancies
Description

Childhood leukemias which cannot be cured by chemotherapy alone may be effectively treated by allogeneic bone marrow transplantation. Moreover, for patients with chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative modality of treatment. Patients who have received hematopoietic stem cells from an HLA matched sibling donor have proven to be less at risk for disease relapse and regimen related toxicity. However, about 70% of patients in need of HSCT do not have an HLA matched sibling donor. This necessitates the search for alternative donors, which may increase the risk of a poor outcome. The nature of the hematopoietic stem cell graft has been implicated as a primary factor determining these outcomes. The standard stem cell graft has been unmanipulated bone marrow, but recently several advantages of T-lymphocyte depleted bone marrow and mobilized peripheral blood progenitor cells (PBPC) have been demonstrated. However, T-cell depletion may increase the risk of infectious complications and leukemic recurrence while an unmanipulated stem cell graft may increase the risk of graft vs. host disease (GVHD). A key element in long range strategies in improving outcomes for patients undergoing matched unrelated donor (MUD) HSCT is to provide the optimal graft. The primary objective of this clinical trial is to estimate the incidence of acute GVHD in pediatric patients with hematologic malignancies who receive HSCT with an unmanipulated marrow graft. The results of this study can be used as the foundation for future trials related to engineering unrelated donor graft.

Conditions

Acute Lymphoblastic Leukemias, Acute Myelocytic Leukemia, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome, Hemoglobinuria, Paroxysmal, Non-Hodgkin Lymphoma

Study of High Dose Cyclophosphamide in Patients With Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
Description

OBJECTIVES: I. Confirm the efficacy demonstrated in a pilot study using high dose cyclophosphamide in patients with severe aplastic anemia. II. Determine whether the addition of filgrastim (G-CSF) to high dose cyclophosphamide shortens the time to recovery in these patients. III. Determine whether this regimen is efficacious in treating paroxysmal nocturnal hemoglobinuria.

Conditions

Aplastic Anemia, Paroxysmal Hemoglobinuria, Nocturnal

The International PNH Interest Group PNH Registry
Description

The aim of this International PNH Interest Group (IPIG) registry is to develop an international database to prospectively collect data on patients with PNH covering clinical outcomes, patient reported outcomes (PROs), and health-resource utilization (HRU) on all enrolled patients, as well as long term safety data.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment
Description

This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with PNH and how the combination compares with 2 existing treatments, one called ravulizumab and the other called eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including: * How effective is the pozelimab + cemdisiran combination compared to ravulizumab? * How effective is pozelimab + cemdisiran combination compared to eculizumab? * What side effects may happen from taking the study drugs? * How much study drugs are in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
Description

The primary objective of the study is: To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy The secondary objectives of the study are to: * Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following: * Transfusion requirements and transfusion parameters * Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50 * Hemoglobin levels * Fatigue as assessed by Clinical Outcome Assessments (COAs) * Health-related quality of life (HRQoL) as assessed by COAs * Safety and tolerability * To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma * To assess the immunogenicity of pozelimab and cemdisiran

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Long-term Safety and Tolerability of Iptacopan in Patients With Paroxysmal Nocturnal Hemoglobinuria
Description

This study is an open-label, single arm, multicenter, roll-over extension study to characterize long-term safety, tolerability and efficacy of iptacopan and to provide access to iptacopan to patients with PNH who have completed Novartis-sponsored Phase 2 or 3 studies with iptacopan

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)
Description

The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
Description

A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Description

The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab
Description

To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria
Description

The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ravulizumab in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Description

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who had never been treated with a complement inhibitor (treatment-naïve).

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)