View clinical trials related to Severe Combined Immunodeficiency.
Filter by:This study aims to determine if a new method can be used to treat Artemis-deficient Severe Combined Immunodeficiency (ART-SCID), a severe form of primary immunodeficiency caused by mutations in the DCLRE1C gene. This method involves transferring a normal copy of the DCLRE1C gene into stem cells of an affected patient. Participants will receive an infusion of stem cells transduced with a self-inactivating lentiviral vector that contains a normal copy of the DCLRE1C gene. Prior to the infusion they will receive sub-ablative, dose-targeted busulfan conditioning. The study will investigate if the procedure is safe, whether it can be done according to the methods described in the protocol, and whether the procedure will provide a normal immune system for the patient. A total of 25 patients will be enrolled at the University of California San Francisco in this single-site trial, and will be followed for 15 years post-infusion. It is hoped that this type of gene transfer may offer improved outcomes for ART-SCID patients who lack a brother or sister who can be used as a donor for stem cell transplantation or who have failed to develop a functioning immune system after a previous stem cell transplant.
The purpose of this study is to evaluate the safety and effectiveness of lentiviral gene transfer treatment at restoring immune function to participants with X-linked severe combined immunodeficiency (XSCID) who are 2 to 40 years of age, and have significant impairment of immunity.
A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with Severe Combined Immune Deficiency undergoing blood stem cell transplantation
This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.
This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.
This is a non-randomized clinical trial using a lentiviral gene transfer vector (or lentivector, LV) to treat patients with X-linked severe combined immunodeficiency (XSCID) who have clinically significant impairment of immunity. We will collect the patient s own stem cells that will be transduced or exposed to the vector carrying a normal copy of the gene. The gene-corrected stem cells will be administered as a one-time infusion. Patients will receive a low-moderate dose of a chemotherapy drug called busulfan (6 mg/kilogram body weight) to allow engraftment of the stem cells. After the infusion, patients will be monitored to see if the treatment is safe and whether their immune system improves. Patients will be monitored for up to 15 years after treatment to assess immune function and the safety of the treatment. XSCID is a genetic disease caused by defects in the common gamma chain, a protein found at the surface of immune cells called lymphocytes, and is necessary to their growth and function. XSCID patients cannot make T-lymphocytes necessary to fight infections, and their B-cells fail to make essential antibodies. Without normal T-and B-lymphocyte function, patients develop fatal infections in infancy unless they receive a bone marrow transplant from a healthy donor. The best type of transplant is from a tissue-matched healthy sibling, but most XSCID patients do not have a tissue-matched sibling and are treated with a transplant from a parent who is only half-matched by tissue typing. While a half-matched transplant from a parent can be lifesaving for an infant with XSCID, a subset of patients fail to achieve sufficient long-lasting restoration of immunity to prevent infections and other chronic problems. Trials of gene transfer treatments using mouse retrovirus vectors for infants with XSCID have been performed and have shown this type of gene transfer can be an alternate approach for significantly restoring immunity to infants with XSCID. However, among the 18 infants with XSCID benefiting long-term from the gene transfer treatment, 5 developed T-lymphocyte leukemia and 1 died of this leukemia. When older children with XSCID were treated with gene transfer, the restoration of immunity was much less than seen in the infants. These observations of gene transfer treatments using mouse retrovirus vectors to treat infants and older patients with XSCID suggest that safer and more effective vectors were needed and that there also may be a need to give chemotherapy or another mode of conditioning to increase engraftment in the marrow of the gene-corrected blood stem cells. Our data and other published studies suggest that lentivectors derived from the human immunodeficiency virus and have the properties of our highly modified vector have a reduced interaction with nearby genes and therefore less of a tendency to activate genes that may lead to cancer formation. This type of lentivector may work better at getting into blood stem cells. The study's purpose is to evaluate the safety and effectiveness of lentiviral gene transfer treatment in restoring immune function to 35 XSCID patients who are 2 to 40 years of age and have significant impairment of immunity. Early evidence for effectiveness will be defined by appearance and expansion in the circulation of the patient s gene-corrected T-lymphocytes with a functional >=c gene and improved laboratory measures of immune function. The primary endpoint for efficacy will be at 2 years after treatment and will include these laboratory parameters plus evidence for clinical benefit. Evidence for safety will focus on the maintenance of a diversity of gene-marked cells and no occurrence of abnormal patterns of production of blood cells or any leukemia or other cancer.
Reduced intensity conditioning followed by allogeneic stem cell transplantation will result in mixed/complete donor chimerism and potentially alter the natural history and outcome of patients with non-malignant diseases.
This protocol (GENEFU) provides a mechanism for the 15-year followup period that the FDA requires for all participants in gene transfer protocols and assures that adequate followup can be maintained for a wide variety of participants on different individual gene therapy protocols at St. Jude Children's Research Hospital. GENEFU serves as an umbrella protocol for long-term follow-up (LTFU) for recipients of gene therapy/gene marked (GT/GM) products at St. Jude Children's Research Hospital. The FDA has recommended methods to assess the risk of delayed adverse events after GT/GM and has provided specific requirements regarding the duration and design of LTFU observations. This protocol is intended to provide LTFU in accordance with the FDA guidelines for those who received a GT/GM product as part of a St. Jude-sponsored clinical trial or compassionate use treatment plan. The protocol calls for a physical examination or general health evaluation and collection of required blood samples annually for up to 15 years after the last receipt of a GT/GM product. Goals will be to obtain clinical histories in order to detect late clinical outcomes suggestive of retroviral or lentiviral disease, including but not limited to cancer/second malignancies, neurologic disorders, autoimmune disorders, and hematologic disorders. Blood samples will be archived and tested when clinically or scientifically indicated, as in the event of development of a second malignancy. This prospective cohort study will utilize descriptive statistics in the analysis of long-term late effects outcomes. It offers a uniform approach to long-term safety monitoring in research participants who have received a gene-transduced product as part of St. Jude-sponsored GT or GM protocols and compassionate use treatment plans.
This study will evaluate patients with abnormal immune function that results in recurrent or unusual infections or chronic inflammation. This may include inherited conditions, such as X-linked severe combined immunodeficiency (XSCID), chronic granulomatous disease (CGD), and leukocyte adhesion deficiency (LAD), or conditions resulting from outside factors, such as graft-versus-host disease (GVHD). The information from this study will be used to establish the pattern and pace of change of the disease and to help develop new treatments. The period of observation and study following enrollment in this study may be for up to one year. In addition these studies may provide the medical information needed to determine eligibility for enrollment in other clinical study protocols and more prolonged follow up. Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls. Normal volunteers undergo a physical examination and provide blood, saliva, and urine samples for immune function studies. Patients' family members provide a medical history, have a physical examination, and give blood and urine samples, and possibly a saliva sample. The samples are used for genetic and routine laboratory studies. Investigators may request tissue samples, such as biopsy specimens, previously removed for medical reasons to be sent to NIH for study. Patients undergo the following tests and procedures: 1. Medical history and physical examination. 2. Blood and urine tests, including analysis for genes involved in immune disorders. 3. Buccal smear (in some patients) for genetic studies. This involves scraping the lining of the mouth near the cheek. 4. Specialized tests to evaluate specific conditions in patients who have an immune disorder that might affect lung function, gum infections or eye problems. These may include chest x-ray, CT scan, breathing function test, dental, eye, and hearing examinations. 5. Follow-up visits of patients with immune problems may occur at 6 months and at one year after the first visit (or more frequently if medically required) to include: - Medical history update - Physical examination - Follow-up on abnormal test results and medical treatments initiated at NIH - Collection of blood, saliva, urine, or wound drainage samples for repeat immune function studies - Tissue study of specimens removed for medical reasons at other institutions besides NIH
This study will examine the role of hereditary factors in different forms of severe combined immunodeficiency (SCID). Patients with immunodeficiencies may be eligible for this study. Candidates include: - Patients with diminished numbers of T cells or NK cells or both, or - Patients with normal T cell and NK cell numbers but diminished T cell, B cell, or NK cell function. Relatives of patients will also be studied. Participants will have blood samples collected for genetic analysis in studies related to SCID at the National Institutes of Health and other institutions. ...