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Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) Clinical Trials References presented on Clinical Trials Search is not intended to be a substitute for proven healthcare advice, trips or professional assistance by using a real medical. We aren't mDs. Always confer with your physician about Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) conditions. Clinical Trials Search.org is a website devoted to listing clinical research studies in human subjects. Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) Clinical research trials and Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) medical trials take place in hundreds of localities across the U.S.. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials usually evaluate the effectualness of new does drugs. The purpose of the studies / projects is to solve specific human health questions. Clinical trials are a popular way for physicians, government agencies, and private sector companies to discover treatments for all sorts of conditions, such as Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID). Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) Clinical Trials and other clinical trials permit volunteers to access healthcare treatment choices before they are available to the general public. Some times the subjects recieve professional assistance for without cost, and every now and again they are compensated for their time. Sometimes there is a cost for a Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) clinical trial. Subjects often receive the most expert healthcare possible for their Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) condition. Risks are a reality, nevertheless, and could include additional or frequent dr. calls, healthcare dangers (perhaps life-jeopardising), and/or the treatment being ineffective. Trials are federally governed with stern guidelines to protect clinical trials subjects.
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Home > "S" Clinical Trials Conditions > Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)  Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
For Condition: Severe Combined Immunodeficiency
Status: Recruiting
Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) ,
Synopsis: This is a clinical trial of gene therapy for X-linked severe combined immunodeficiency (XSCID), a genetic disease caused by defects in a protein called the common gamma chain, which is normally on the surface of immune cells called lymphocytes. XSCID patients cannot make T lymphocytes, and their B lymphocytes fail to make essential antibodies for fighting infections. Without T and B lymphocytes patients develop fatal infections in infancy unless they are rescued by a bone marrow transplant from a healthy donor. However, even transplanted patients may achieve only partial immune recovery and still suffer from many infections, auto-immunity and/or and poor growth. A recent, successful trial in France used gene therapy instead of bone marrow transplantation for infants with XSCID. This experience indicates that gene therapy can provide clinical benefit to XSCID patients. We will enroll six older XSCID patients (2-20 years-old_, who have previously received at least one bone marrow transplant, but still have poor T and B lymphocyte function that compromises their quality of life. Before enrollment, these subjects will have had some of their own blood-forming stem cells harvested and frozen in a blood bank. These cells have a defective gene, but a correct copy of the gene will be inserted while the cells are grown in sterile conditions outside the patient's body. To do this, the cells will be unfrozen and exposed for four days in a row to growth factors and particles of a retrovirus we have constructed and tested called "GALV MFGS-gc." Retrovirus particles will attach to the patient cells and introduce a correct copy of the common gamma chain gene into cells capable of growing into all types of blood cells, including T and B ymphocytes. Each XSCID patient enrolled in the study will receive a single dose of his own cells that have been modified by the GALV MFGS-gc treatment. After this, the patients will be monitored to find out if the treatment is safe and to see if their immune function improves. Study endpoints are (1) efficient and safe clinical-scale correction of cells from XSCID patients; (2) administration of treated cells to six subjects: and (3) year follow-up of the treated subjects to see how many of their cells have taken up the correct copy of the gene, how many new T and B lymphocytes express a normal common gamma chain, and whether the patients' immune function and general health improve.
Details: This is a Phase I/II clinical trial of ex vivo hematopoietic stem cell (HSC) gene therapy for X-linked severe combined immunodeficiency (XSCID). XSCID results from defects in the IL2RG gene encoding the common gamma chain (gc) shared by receptors for Interleukin 2 (IL-2), IL-4, IL-7, IL-9, IL-15 and IL-21. XSCID patients generally lack T-lymphocytes and NK cells, and their B-lymphocytes fail to make essential antibodies. XSCID is fatal in infancy without immune reconstitution, such as by allogeneic bone marrow transplantation (BMT). However, many transplanted patients achieve only partial immune reconstitution, and consequently have recurrent infections, autoimmunity and/or poor growth. Recent successful retroviral gene therapy instead of BMT for infants with XSCID indicates that ex vivo gene therapy can provide clinical benefit to XSCID patients, although leukemia occurred in two of the treated patients indicating that there are significant risks with gene therapy. We will enroll six older XSCID patients (2-20 years-old; greater than or equal to 15 kg body weight), who have had attempted BMT, but who have persistent T-lymphocyte and B-lymphocyte impairments that compromise their quality of life. Prior to enrollment, each case will be presented for review and risk/benefit assessment by the IRB and regulatory agencies. These subjects will have had autologous CD34+ HSC mobilized by treatment with granulocyte colony stimulating factor (G-CSF), collected from peripheral blood by apheresis, immune selected and cryopreserved in sufficient numbers to achieve entry criteria (greater than or equal to 1.0 x 10(6) CD34+ HSC/kg body weight). HSC procurement will be conducted under a separate, approved and active NIH protocol, 94-I-0073, 'Recruitment of peripheral blood hematopoietic progenitors by granulocyte colony stimulating factor [G-CSF]'. Autologous CD34+ HSC will be subjected to four daily transductions ex vivo with the gibbon ape leukemia virus (GALV) envelope-pseudotyped, replication-defective, murine onco-retrovirus vector, MFGS-gc that encodes the common gamma chain. Transductions will occur in flexible gas-permeable plastic containers using serum-free medium supplemented with 1% human serum albumin and five recombinant growth factors (50 ng/ml Flt3-L, 50 ng/ml SCF, 50 ng/ml TPO, 25 ng/ml IL-6, and 5 ng/ml IL-3). Each subject will receive a single infusion of transduced HSC. Subjects will be monitored for safety and efficacy; the latter evidenced by new development of autologous transduced lymphocytes with functional gc. Study endpoints are (1) efficient and safe clinical-scale transduction of HSC from post-BMT XSCID subjects; (2) administration of transduced HSC to six subjects; and (3) 3 year follow up of treated subjects to monitor vector sequence distribution, gc expression in hematopoietic lineages, and lymphocyte numbers and function; as well as general health and immune status.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: Patients must have XSCID as defined by either a deleterious mutation in IL2RG, the absence of or less than 5% of normal detectable gc protein, or evidence of functionally defective gc protein. Patients must be between 2 and 20 years of age. Patients must weigh at least 15 kg. Patients will have evidence of combined B-cell and T-cell immune deficiency over at least a 6 month period despite previous allogeneic BMT at least 18 months prior to study entry. T-cell immune deficiency is defined as one or more of the following: Total T-cell count less than 500/ul; less than 50% of normal value for in vitro mitogen stimulation; or absent proliferation in vitro to antigens. B-cell immune deficiency is defined as one or more of the following: IgM, IgA or IgE values which are 2 or more standard deviations below the established value for normal, IgG values falling to less than 30% of normal during unintended interruptions or delay in the periodic administration of IVIG; or documented failure to respond to a specific antigen challenge. Patients must less than or equal to 3% of their mobilized CD34+ cells deriving from their allogeneic bone marrow donor. EXCLUSION CRITERIA: Any current or preexisting hematologic malignancy. Current treatment with any chemotherapeutic agent. Current treatment with any immunosuppressive agent, excluding corticosteroids. Documented HIV-1 infection. Documented Hepatitis B infection. Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or known genotype of the subject conferring a predisposition to cancer.
Total Enrollment: 6
Location and Contact Information:
National Institute of Allergy and Infectious Diseases (NIAID) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 020057; 02-I-0057
Study Start Date: December 10, 2001
Record last reviewed: January 6, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00028236
Other Severe Combined Immunodeficiency Studies:
1. Cord Blood Stem Cell Transplantation Study (COBLT)
2. Use of G-CSF to Obtain Blood Cell Precursors
3. Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
4. Genetic Basis of Immunodeficiency
5. Influences on Female Adolescents' Decisions Regarding Testing for Carrier Status of XSCID
Related Studies:
Other Severe Combined Immunodeficiency Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
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