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X-Linked Severe Combined Immunodeficiency - ClinicalTrials.gov

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Last Updated: 24 January 2022

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Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency

On day 1 and dose adjusted to target their bone marrow, patients will be given a total busulfan dose of 6 mg/kg/body weight as 3 mg/kg body weight, followed by a single infusion of autologous transduced CD34+HSC. However, the overwhelming majority of patients with XSCID do not have a matching sibling donor, and in those patients, the most appropriate treatment is to perform a transplant of T-lyocyte depleted bone marrow from a parent. In general, a parent will be only half-matched by HLA tissue typing to the affected child, which is called haploidentical. Whether or not any conditioning is employed, a haploidentical transplant for XSCID has a significantly poorer prognosis than a matched sibling donor transplant. Following haploidentical transplantation, XSCID patients have been found to have a wide variety of partial immune reconstitution and that reconstitution can fade over time in some patients. Despite previous haploidentical hematopoietic stem cell transplantation and absence of a HLA-matched sibling donor, we recommend offering gene transfer therapy to XSCID patients3 2 years of age with clinically significant immune defects, particularly those who have clinically significant alterations of immunity and who do not have a HLA-matched sibling donor. In addition, new research into gene transfer therapy of older XSCID patients with MLV-based vectors revealed the additional issue of inadequate expansion of gene corrected T- lymphocytes to infants' very high levels. Based on our previous work with older patients with XSCID who are either partially haploidentical donor enrolled or who failed to engraft after several attempts at haploidentical donor transplantation, there seems to be a significant barrier to autologous gene corrected autologous lymphocyte production, as shown by the inability of producing sufficient numbers of gene corrected autologous lymphocytes. The patients for this study may have some degree of lymphoid immunity either from donor lymphocytes or their own partially functional or autologous lymphocyes that may have played a role in the poor engraftment and function of their previous haploid HSC transplant. The first choice source of HSC for this research will be Mobilized peripheral blood stem cells isolated by apheresis, but patients who are unable to obtain sufficient HSC by this method will be treated by bone marrow biopsy. Patients will be treated with autologous CD34+ HSC at the NIH under a separate, currently approved stem cell collection protocol, according to a NIH stem cell collection protocol. If there are at least 3 x 106 per kilogram body weight autologous CD34+HSC available for gene transfer transduction, a patient participating in this program will not proceed to transfer of autologous HSC or to busulfan conditioning until at least 3 x 106 per kilogram body weight autologous CD34+HSC is available for gene transfer transduction. Following the conditioning and gene exchange therapy, subjects will be nourished through any period of cytopenia and monitored for safety and effectiveness of the gene transfer therapy.

Source link: https://clinicaltrials.gov/ct2/show/NCT01306019


A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells

This research will explore the first use of a SIN lentiviral vector for the treatment of SCID-X1 in the treatment of SCID-X1 and may lead to a new form of therapy that may be applicable to the majority of newly diagnosed patients. OBJECTIVES Assess the safety, availability, and efficacy of lentiviral gene transfer in newly diagnosed SCID-X1 patients transplanted with autologous CD34+ cells transplanted with a self-inactivating lentiviral vector expressing a c gene in newly diagnosed SCID-X1 patients transplanted with an autologous gene transplant with a self-inactivating lentiviral vector expressing a corresponding c gene transduced At least 2 of the following three criteria are present: correlating busulfan and its metabolite pharmacokinetics with toxicity, emulation of vector-transduced cells, and event-free survival and overall survival. For a total of 2 doses in order to achieve a cumulative busulfan area with a curve of 22 mg/hr/L, Eva evaluate the safety of busulfan dose-targeting with busulfan administration every 24 hours for a total of two doses. If the vector copy number is greater than 5 copies per T cell in any patient at any time, the vector copy number in sorted T-cells will be tested as a safety measure and will be reported to the FDA as a potential safety measure and will be reported to the FDA if the vector copy number is greater than 5 copies per T cell in any patient at any time.

Source link: https://clinicaltrials.gov/ct2/show/NCT01512888

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions