View clinical trials related to Severe Combined Immunodeficiency.
Filter by:SCID-X1 is a genetic disorder of blood cells caused by DNA changes in a gene that is required for the normal development of the human immune system. The purpose of this study is to determine if a new method, called lentiviral gene transfer, can be used to treat SCID-X1. This method involves transferring a normal copy of the common gamma chain gene into the participant's bone marrow stem cells. The investigators want to determine if the procedure is safe, whether it can be done according to the methods they have developed, and whether the procedure will provide a normal immune system for the patient. It is hoped that this type of gene transfer may offer a new way to treat children with SCID-X1 that do not have a brother or sister who can be used as a donor for stem cell transplantation.
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of EZN-2279 in patients with ADA-deficient combined immunodeficiency currently being treated with Adagen.
X-linked severe combined immunodeficiency (SCID-X1) is an inherited disorder that results in failure of development of the immune system in boys. This trial aims to treat SCID-X1 patients using gene therapy to replace the defective gene.
This is a historically controlled, non-randomized Phase I/II clinical trial to assess the safety and efficacy of autologous transplantation of CD34+ hematopoietic stem/progenitor cells (HSPCs), obtained from infants affected by ADA-SCID, following transduction of the HSPCs with a lentiviral vector (LV) carrying the human ADA complementary DNA (cDNA) under the control of the elongation factor 1 alpha shortened (EFS) promoter. Subjects treated in the trial receive the infusion of autologous, transduced cells following marrow cytoreduction with busulfan. The outcomes are compared to those observed in a historical control group of patients who received an allogeneic hematopoietic stem cell transplant (HSCT). This Phase I/II clinical trial will be performed at Great Ormond Street Hospital (GOSH), London, United Kingdom.
Individuals with a past diagnosis of severe combined immune deficiency (including many cases of "leaky SCID", Omenn syndrome, and reticular dysgenesis) who have undergone blood and marrow transplant, gene therapy, or enzyme replacement in the past may be eligible for this study. The purpose of study is to look backwards at what has already been done in the. Over 800 patients with SCID are expected to be enrolled, making this one of the largest studies ever to describe outcomes for patients with SCID treated at many different hospitals around North America.
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. ...
Adenosine deaminase deficiency is an inherited disorder that results in severe abnormalities of the immune system and leaves children unable to fight infection. This trial aims to treat adenosine deaminase deficiency patients using gene therapy.
This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study. Children will be divided into three strata: - Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function - Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and - Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy. Each Group/Cohort Stratum will be analyzed separately.
Background: - Severe combined immunodeficiency (SCID) is a rare inherited disorder in which certain white blood cells have impaired function and are unable to properly fight infections. SCID typically appears within the first year of life and is characterized by multiple, recurrent severe infections. More than 10 percent of all cases of SCID involve a deficiency of an enzyme called adenosine deaminase (ADA), and these SCID patients also tend to have impaired brain function or psychiatric disorders. Researchers are attempting to treat ADA-SCID patients with an experimental gene therapy, and a research protocol has been established for those who are participating in this therapy. - Little is known about quality of life in individuals with ADA-SCID, but researchers believe that the effects of the disease and the treatments may cause a decreased quality of life in both patients and their parents. Another potential cause of decreased quality of life in ADA-SCID is the associated psychiatric and neurological problems caused by the disease. Researchers are interested in studying quality of life in individuals with ADA-SCID and their parents to provide more information about the disease. Objectives: - To evaluate whether gene therapy alters the quality of life or neuropsychiatric status of children with ADA-SCID. - To monitor for intellectual, attention, memory, or specific learning disorders in children with ADA-SCID. - To evaluate whether undergoing gene therapy has an effect on parenting stress of parents whose children have ADA-SCID. Eligibility: - Children who are participating in the ADA-SCID gene therapy research protocol (01-HG-0189). - Parents of children who are participating in the ADA-SCID gene therapy research protocol (01-HG-0189). Design: - All of the testing and questionnaires will be done in the pediatric or adult clinic. - Participating children will have tests of intelligence, manual dexterity, reaction time, basic reading and arithmetic skills, speech, and memory. These tests will be given before the start of the therapy, and then once a year for 5 years. - Participating children will also complete questionnaires on quality of life. These questionnaires will be given before the start of the therapy, 3 months and 6 months after the therapy, and then every 6 months for a total of 5 years. - Additional psychological tests may be given at the discretion of the study researchers. - Parents will complete questionnaires to provide background medical information and report on quality of life and parental stress. The background information questionnaires will be given at the start of the therapy and then once a year for 5 years, the parental stress questionnaires will be given at the start of the therapy and then every 6 months for 5 years, and the quality of life questionnaires will be given at the same time as the child quality of life questionnaires. - This protocol is separate from the gene therapy treatment protocol.
The goal of this study is to develop a novel approach to hematopoietic stem cell transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune reconstitution. Rather than classic chemotherapeutic agents, the investigators will utilize a targeted stem cell mobilizer, plerixafor, in combination with alemtuzumab, a monoclonal antibody. Correlative scientific questions will include: 1) efficacy and characteristics of host stem cell mobilization; and 2) alemtuzumab pharmacokinetics in very young children.