48 Clinical Trials for Various Conditions
The investigators want to study if lower doses of chemotherapy will help babies with SCID to achieve good immunity with less short and long-term risks of complications after transplantation. This trial identifies babies with types of immune deficiencies that are most likely to succeed with this approach and offers them transplant early in life before they get severe infections or later if their infections are under control. It includes only patients receiving unrelated or mismatched related donor transplants. The study will test if patients receiving transplant using either a low dose busulfan or a medium dose busulfan will have immune recovery of both T and B cells, measured by the ability to respond to immunizations after transplant. The exact regimen depends on the subtype of SCID the patient has. Donors used for transplant must be unrelated or half-matched related (haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T cells removed, using a newer, experimental approach of a well-established technology. Once the stem cell transplant is completed, patients will be followed for 3 years. Approximately 9-18 months after the transplant, vaccinations will be administered, and a blood test measuring whether your child's body has responded to the vaccine will be collected.
Infants with severe combined immunodeficiency (SCID) have a profound decrease in number and function of immune cells, and therefore remain highly vulnerable to infection. If not corrected this often leads to death. Hematopoietic cell transplantation (HCT) from matched sibling donor is the standard treatment for these patients, unfortunately though; most SCID patients lack a sibling donor. Building upon experience and existing data, the investigators are proposing a trial the goals of which are: to provide a conditioning regimen that is well tolerated, and provision of immune cells that altogether should establish rapid immune recovery providing protection from life threatening infections without increasing the risk of dangerous Graft-Versus-Host-Disease. Primary Objectives 1. To evaluate the safety of a TCRα/β/CD19-depleted graft with CD45RA-depleted DLI in infants with SCID 2. To estimate overall survival at 1 year post transplantation Exploratory Objectives 1. To evaluate the significant donor T cell reconstitution of a TCRα/β/CD19 depleted graft with CD45RA-depleted DLI at 1 year (+/-2 weeks). 2. To evaluate engraftment at day 30, 100, month 6, and years 1 to 10 post HCT. 3. To evaluate B cell reconstitution at years 1 to 10 post HCT. 4. To evaluate biomarkers of immune reconstitution at day 30, 60 100, month 6 and years 1 to 10; e.g. immunophenotype (including epigenetic profiling) of T, B, and NK cells, and assays to determine their function. 5. To evaluate clinical outcomes, post HCT. 6. To define the incidence and severity of acute (at day 100, month 6), and chronic (month 6, 12, 24) GVHD following HCT.
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
Study Design: SCID infants receiving an unconditioned haploidentical transplant will be started on Sirolimus (0.05 mg/kg/day) day -5 for Acute Graft-Versus-Host Disease (aGVHD) prophylaxis. Sirolimus levels will be monitored with goal sirolimus trough level of 5-8 ng/mL. Patients will be monitored for signs of aGVHD as defined by UCSF SOP CL 221.06 through day +100. Sirolimus will be tapered once T-regulatory cell to CD4 effector cell ratio is \> or = 9%. Setting: Inpatient BMT Unit Benioff Children's Hospital at UCSF Medical Center Study Subjects: 15 infants with diagnosis of maternally engrafted T cells SCID by CA Newborn screen receiving unconditioned haploidentical HSCT Main Outcome Measures: Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by SOP CL 221.06 by Day +100. Hypothesis 1. Patients placed on sirolimus prophylaxis will have lower incidence of aGVHD compared to historical controls. Hypothesis 2. Lower doses of sirolimus milligram per kilogram will be required to maintain goal troughs of 5-8 ng/mL.
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD), 2) unrelated cord blood donor, or 3) a haplo-identical (parental) donor (in descending order of preference).Patients will receive a novel conditioning regimen with Busulfan, Fludarabine and Anti-thymocyte globulin (ATG) followed by an unrelated donor hematopoietic stem cell transplant (HSCT) with T-cell depletion using the CliniMACS device.
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.
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.
Researchers are working on ways to treat SCID patients who don't have a matched brother or sister. One of the goals is to avoid the problems that happen with stem cell transplant from parents and unrelated people, such as repeat transplants, incomplete cure of the immune system, exposure to chemotherapy, and graft versus host disease. The idea behind gene transfer is to replace the broken gene by putting a piece of genetic material (DNA) that has the normal gene into the child's cells. Gene transfer can only be done if we know which gene is missing or broken in the patient. For SCID-X1, gene transfer has been done in the laboratory and in two previous clinical trials by inserting the normal gene into stem cells from bone marrow. The bone marrow is the "factory" inside the bones that creates blood and immune cells. So fixing the gene in the bone marrow stem cells should fix the immune problem, without giving chemotherapy and without risk of graft versus host disease, because the child's own cells are used, rather than another person's. Out of the 20 subjects enrolled in the two previous trials, 18 are alive with better immune systems after gene transfer. Two of the surviving subjects received gene corrected cells over 10 years ago. Gene transfer is still research for two reasons. One is that not enough children have been studied to tell if the procedure is consistently successful. Of the 20 children enrolled in the previous two trials, one child did not have correction of the immune system, and died of complications after undergoing stem cell transplant. The second important reason why gene transfer is research is that we are still learning about the side effects of gene transfer and how to do gene transfer safely. In the last two trials, 5 children have experienced a serious side effect. These children developed leukemia related to the gene transfer itself. Leukemia is a cancer of the white blood cells, a condition where a few white blood cells grow out of control. Of these children, 4 of the 5 have received chemotherapy (medication to treat cancer) and are currently in remission (no leukemia can be found by sensitive testing), whereas one died of gene transfer-related leukemia.
The goal of the proposed research is to establish the validity of a newborn screening method for severe combined immunodeficiency (SCID). The assay to be used is developed on the basis of PCR quantification of T-cell receptor excision circles (TRECs) that is absent in SCID patients, thus correlating with the disease
This study will evaluate a new method for delivering gene transfer therapy to patients with severe combined immunodeficiency disease (SCID) due to a defective adenosine deaminase (ADA) gene. This gene codes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections. Some patients with this disease receive enzyme replacement therapy with weekly injections of the drug PEG-ADA (ADAGEN). This drug may increase the number of immune cells and reduce infections, but it is not a cure. Gene transfer therapy, in which a normal ADA gene is inserted into the patient s cells, attempts to correct the underlying cause of disease. This therapy has been tried in a small number of patients with varying degrees of success. In this study, the gene will be inserted into the patient s stem cells (cells produced by the bone marrow that mature into the different blood components white cells, red cells and platelets). Patients with ADA deficiency and SCID who are taking PEG-ADA and are not candidates for HLA-identical sibling donor bone marrow transplantation may be eligible for this study. Participants will be admitted to the NIH Clinical Center for 2 to 3 days. Stem cells will be collected either from cord blood (in newborn patients) or from the bone marrow. The bone marrow procedure is done under light sedation or general anesthesia. It involves drawing a small amount of marrow through a needle inserted into the hip bone. The stem cells in the marrow will be grown in the laboratory and a normal human ADA gene will be transferred into them through a special type of disabled mouse virus. A few days later, the patient will receive the ADA-corrected cells through an infusion in the vein that will last from 10 minutes to 2 hours. Patients will be evaluated periodically for immune function with blood tests, skin tests, and reactions to tetanus, diphtheria, H. influenza B and S. pneumoniae vaccinations. The survival of ADA-corrected cells will be monitored through blood tests. The number and amount of blood tests will depend on the patient s age, weight and health, but is expected that blood will not be drawn more than twice a month. Patients will also undergo bone marrow biopsy aspirate (as described above) twice a year. Patients will be followed once a year indefinitely to evaluate the long-term effects of therapy.
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from mobilized peripheral blood (mPB) of ADA-deficient SCID infants and children following human ADA gene transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.
Background: Severe combined immune deficiency (SCID) is a group of conditions where the immune system does not work properly. The only cure for most SCIDs is a stem cell transplant (getting cells from a donor). These transplants can have serious complications. Before the transplant, people often get high doses of drugs and radiation to prepare the body to accept the cells from the donor. Researchers want to see if low doses of drugs alone without radiation work just as well as low doses of drugs with radiation for SCID patients getting stem cell transplants. Objective: To test a set of drugs with or without radiation given before a stem cell transplant. Eligibility: People ages 3-40 who have SCID and who have a stem cell donor - either related or unrelated. Design: Participants will be admitted to the hospital 10 days before transplant. They will undergo: medical history medication review physical exam blood and urine tests (may include a 24-hour urine collection) heart, lung, and breathing tests imaging scans bone marrow sample nutrition assessment dental exam eye exam meeting with a social worker. Participants will get a plastic port called a central line. It is a hollow tube that is placed in the upper chest. It will be used to give medicines and take blood. All participants will take chemotherapy drugs. Some will get radiation. Participants will have a stem cell transplant. They will get the cells as an infusion through their central line. They will stay in the hospital for 30 days after transplant. Participants must stay within 1 hour of NIH for 3 months after transplant. During this time, they will have follow-up visits at NIH at least once a week. Then they will have follow-up visits once or twice a year for 5-6 years.
This observational long-term follow-up study is designed to collect safety and efficacy data from ADA-SCID patients previously treated with autologous ex vivo gene therapy products based on the EFS-ADA LV encoding for human adenosine deaminase (ADA) gene (EFS-ADA LV), as part of the OTL-101 clinical development program. No investigational medicinal product will be administered to these patients as part of the OTL-101-6 study.
This registry study is being conducted in patients with adenosine deaminase severe combined immune deficiency (ADA-SCID) who require enzyme replacement therapy (ERT) treatment with Revcovi. Data on safety and on measures of efficacy are collected.
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 24 newly diagnosed 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.
This is a phase I/II open label multi-center study in which patients will receive low dose targeted busulfan followed by infusion of autologous CD34+ selected bone marrow or mobilized peripheral blood cells transduced with the G2SCID vector. Subjects will be enrolled over 3 years and be followed for 2 years post-infusion on this protocol, then followed long-term on a separate long-term follow-up protocol. Enrollment of subjects will be agreed upon by representatives of both sites. Data will be collected uniformly from both sites through an electronic capture system and key laboratory studies will be centralized. Harvest, cellular manufacturing and infusion will occur at each site using the same SOPs. Key aspects of cellular product characterization will be centralized
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at least 24 hours following the completion of reduced intensity conditioning. For subjects who successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge from hospital, the subjects will be seen at regular intervals to review their history, perform examinations and draw blood samples to assess immunity and safety.
This study will evaluate the efficacy of a newly developed serious game, SCI HARD, to enhance self-management skills, self-reported health behaviors, and quality of life among adolescents and young adults with spinal cord injury and disease (SCI/D). SCI HARD was designed by the project PI, Dr. Meade, in collaboration with the UM3D (University of Michigan three dimensional) Lab between 2010 and 2013 with funding from a NIDRR (National Institute on Disability and Rehabilitation Research) Field Initiated Development Grant to assist persons with SCI develop and apply the necessary skills to keep their bodies healthy while managing the many aspects of SCI care. The study makes a unique contribution to rehabilitation by emphasizing the concepts of personal responsibility and control over one's health and life as a whole. By selecting an innovative approach for program implementation, we also attempt to address the high cost of care delivery and lack of health care access to underserved populations with SCI/D living across the United States (US). H1: SCI Hard participants will show greater improvements in problem solving skills, healthy attitudes about disability, and SCI Self-efficacy than will control group members; these improvements will be sustained over time within and between groups. H2: SCI Hard participants will endorse more positive health behaviors than control group members; these improvements will be sustained over time within and between groups. H3: SCI Hard participants will have higher levels of QOL than control group members; these differences will be sustained over time within and between groups. H4: Among SCI Hard participants, dosage of game play will be related to degree of change in self-management skills, health behaviors and QOL.
This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and re-infused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.
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.
The purpose of this study is to evaluate specific approaches used to prevent/reduce influenza transmission in the SCI/D System of Care in response to the 2009 H1N1 pandemic, including assessing infection control strategies used by SCI staff and guidance provided by local infection control units. Due to the rapid spread of and uncertainties about the H1N1 virus, we will evaluate patient's beliefs, behaviors, and information seeking strategies (e.g., social media). These findings will lend to the understanding of ways to handle emergent issues, such as the H1N1 pandemic, in special populations.
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.
Severe combined immune deficiency (SCID) may result from inherited deficiency of the enzyme adenosine deaminase (ADA). Children with ADA-deficient SCID often die from infections in infancy, unless treated with either a bone marrow transplant or with ongoing injections of PEG-ADA (Adagen) enzyme replacement therapy. Successful BMT requires the availability of a matched sibling donor for greatest success, and treatment using bone marrow from a less-well matched donor may have a higher rate of complications. PEG-ADA may restore and sustain immunity for many years, but is very expensive and requires injections 1-2 times per week on an ongoing basis. This clinical trial is evaluating the efficacy and safety of an alternative approach, by adding a normal copy of the human ADA gene into stem cells from the bone marrow of patients with ADA-deficient SCID. Eligible patients with ADA-deficient SCID, lacking a matched sibling donor, will be eligible if they meet entry criteria for adequate organ function and absence of active infections and following the informed consent process. Bone marrow will be collected from the back of the pelvis from the patients and processed in the laboratory to isolate the stem cells and add the human ADA gene using a retroviral vector. The patients will receive a moderate dosage of busulfan, a chemotherapy agent that eliminates some of the bone marrow stem cells in the patient, to "make space" for the gene-corrected stem cells to grow once they are given back by IV. Patients will be followed for two years to assess the potentially beneficial effects of the procedure on the function of their immune system and to assess possible side-effects. This gene transfer approach may provide a better and safer alternative for treatment of patients with ADA-deficient SCID.
The Veteran's Health Administration (VHA) is a national leader in using distance technology to monitor patients' self-care via an in-home messaging device with disease management protocols (DMPs). No such DMPs exist for the community dwelling spinal cord injury/disorders (SCI/D) population. Our objective is to develop the tools necessary for implementing a new home telehealth program to manage community-dwelling veterans with SCI/D at high risk of developing pressure ulcers (PrUs).
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched (up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them are rat IgG1 (immunoglobulin G1) antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of \>90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. Campath 1H, Alemtuzumab, has been licensed to treat B-cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with SCID, in whom the use of conventional chemotherapeutic agents for conditioning may produce or aggravate unacceptable and even lethal short term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial GvHD prophylaxis. Additional Graft versus Host Disease (GvHD) prophylaxis may be provided by administration of FK506.
The purpose of this study is to determine if immunophilin ligands may have the potential to reverse hair loss.
This study will monitor the long-term effects of gene therapy in patients with severe combined immunodeficiency disease (SCID) due to a deficiency in an enzyme called adenosine deaminase (ADA). It will also follow the course of disease in children who are not receiving gene therapy, but may have received enzyme replacement therapy with the drug PEG-ADA. ADA is essential for the growth and proper functioning of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are, therefore, immune deficient and vulnerable to frequent infections. Injections of PEG-ADA may increase the number of immune cells and reduce infections, but this enzyme replacement therapy is not a definitive cure. In addition, patients may become resistant or allergic to the drug. Gene therapy, in which a normal ADA gene is inserted into the patient's cells, attempts to correcting the underlying cause of disease. Patients with SCID due to ADA deficiency may be eligible for this study. Patients may or may not have received enzyme replacement therapy or gene transfer therapy, or both. Participants will have follow-up visits at the National Institutes of Health in Bethesda, Maryland, at least once a year for a physical examination, blood tests, and possibly the following additional procedures to evaluate immune function: 1. Bone marrow sampling - A small amount of marrow from the hip bone is drawn (aspirated) through a needle. The procedure can be done under local anesthesia or light sedation. 2. Injection of small amounts of fluids into the arm to study if the patient's lymphocytes respond normally. 3. Administration of vaccination shots. 4. Collection of white blood cells through apheresis - Whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the red cells, platelets and plasma are returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm. 5. Blood drawings to obtain and study the patient's lymphocytes.
This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.
This study will use a randomized controlled design with an active attention control group to evaluate an intervention intended to reduce social isolation and loneliness in persons with SCI/D. The intervention, Caring Connections, is a peer-based intervention which is important because peers with SCI/D play an important role in improving quality of life, mental health, and social health in persons with SCI/D.
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.