Active clinical trials for "Leukocyte-Adhesion Deficiency Syndrome"

The primary objective of this extension study is to assess the long-term safety and efficacy of AVTX-803 in subjects with LAD II (SLC35C1-CDG).

The primary objective of this study is to evaluate the efficacy and safety of AVTX-803 compared to withdrawal in patients with Leukocyte Adhesion Deficiency, Type II (LAD II).

OBJECTIVES: I. Provide curative immunoreconstituting allogeneic bone marrow transplantation for patients with primary immunodeficiencies. II. Determine relevant outcomes of this treatment in these patients including quality of survival, extent of morbidity and mortality from complications of the treatment (e.g., graft versus host disease, regimen related toxicities, B- cell lymphoproliferative disease), and completeness of functional immunoreconstitution.

This study will evaluate the safety and effectiveness of the drug, interferon gamma, in treating leukocyte adhesion deficiency type I (LAD I). Patients with this inherited immune disorder do not have enough proteins called adhesion molecules on their infection-fighting white blood cells, impairing the ability of these cells to get to the site of infection. As a result, patients have recurrent infections of soft tissues, such as the skin, gums and gastrointestinal tract, and poor wound healing. Infants with severe LAD I often die from multiple infections. Interferon gamma may increase the number of adhesion molecules on white blood cells, and thus improve their function. Patients with LAD I who weigh more than 13 kilograms (28.5 pounds) may be eligible for this study. Candidates will have personal and family medical histories taken, a physical examination, blood and urine tests and a chest X-ray or computed tomography (CT) scan. Participants will receive injections of interferon gamma under the skin 3 times a week for 3 months. Adult patients will be taught how to give their own injections (similar to insulin injections for diabetes) and parents will be taught how to administer the shots to their child. Blood samples, usually be between 30 to 90 milliliters (2 to 6 tablespoons), will be drawn just before starting medication and again 1 day, 1 week, 1 month, 3 months and 4 months after therapy begins. At these same time intervals, patients will provide a salt-water mouth rinse specimen, which will be tested for changes in the number of white blood cells during interferon gamma treatment. Patients will be admitted to the NIH Clinical Center for inpatient evaluations at the start of therapy and again after 1 week, 1month, 3 months and 4 months. The initial screening visit will take a few days and subsequent visits will take 1 to 2 days.

This study will investigate the safety and effectiveness of a modified stem cell transplant procedure for treating leukocyte adhesion deficiency (LAD). LAD is an inherited blood disorder of leukocytes (infection-fighting white blood cells) that leaves patients vulnerable to life-threatening infections. Transplantation of donated stem cells (cells produced by the bone marrow that mature into blood cells) can improve the immune system of patients with LAD. However, this procedure carries a significant risk of death, particularly in patients with active infection because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, T-cells (a type of white blood cell) from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to destroy them. To try to reduce these risks, the donor's T-cells will be removed from the rest of the stem cells to be transplanted. Patients with LAD who weigh at least 12 kg (26.4 LB), who do not have an active infection, and who have a family member that is a well-matched donor may be eligible for this study. Pregnant or breast feeding women may not participate. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays or computed tomography (CT) scans of the body, and dental and eye examinations. They will fill out questionnaires that measure emotional well being, quality of life and intelligence (the ability to learn and understand). Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to move stem cells from the bone marrow to the bloodstream. The stem cells will be collected by apheresis, where blood is drawn through a needle placed in one arm and pumped into a machine separating and removing the required cells. The rest of the blood is then returned through a needle in the other arm. Before the transplant, a central venous line (large plastic tube) is placed into a major vein. This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells, give medications, transfuse blood, if needed, and withdraw blood samples. Several days before the transplant procedure, patients will begin a conditioning regimen of low-dose chemotherapy with cyclophosphamide, fludarabine, and Campath 1H. When the conditioning therapy is completed, the stem cells will be infused. To help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein starting 1 month after the transplant procedure. The average hospital stay for stem cell transplantation is 21 days. After discharge, patients will return for follow-up clinic visits weekly or twice weekly for 2 to 3 months. These visits will include a symptom check, physical examination, and blood tests. Subsequent visits will be scheduled at 4, 6, 9, and 12 months after the transplant, or more often if required, and then yearly

Study of ORL-1F in Patients With Leukocyte Adhesion Deficiency Type II

This study will provide long-term monitoring of two patients who received gene therapy for leukocyte adherence deficiency (LAD) under the Food and Drug Administration investigational new drug study BB-IND-7949. The IND protocol has been closed. No other patients are eligible for this study. Patients previously enrolled in BB-IND-7949 (Retrovirus-Mediated Transfer of the cDNA for Human CD18 into Peripheral Blood Repopulating cells of Patients with Leukocyte Adherence Deficiency) will be followed at least yearly for an indefinite period of time to evaluate their medical status and look for treatment side effects. The follow-up visits at the NIH Clinical Center will involve the following: Interview regarding health status during the past year Blood draw of approximately 15 milliliters for 3 years, then 5 ml annually thereafter for studies related to LAD and to make sure no unexpected effects of gene therapy have occurred The blood samples collected at the follow-up visits will be frozen and stored. If a serious medical problem arises, the sample may be checked for replication competent virus. If the gene therapy is suspected to be related to a medical problem, investigation may include a review of the patient's medical records or collection of additional blood or tissues for testing. If the patient should die, the family will be asked permission to perform an autopsy, regardless of the cause of death. Tissues taken at autopsy will be tested for any long-term effects from the gene therapy.

OBJECTIVES: I. Identify the molecular defects responsible for primary immunodeficiency disorders. II. Explore the mutations within each syndrome to better understand the genetics of these disorders. III. Study the function of the Wiskott-Aldrich syndrome proteins (WASP). IV. Design methods to identify carriers and for prenatal diagnosis. V. Explore new avenues for therapy.