Clinical Trial: Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Ex Vivo Retroviral Gene Transfer For Treatment of X-Linked Severe Combined Immunodeficiency (XSCID)

Brief Summary: 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 eight older XSCID patients (1.5-20 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 lymphocytes. XSCID patients who are enrolled in the study will receive a single dose of their own cells that have been modified by the GALV MFGS-gc treatment and also will be given another drug called palifermin to help prevent side eff

Detailed Summary:

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.

We will enroll eight older XSCID patients (1.5-20 years-old; greater than or equal to 12 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, 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 transduced 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
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: December 17, 2001
Date Started: December 10, 2001
Date Completion:
Last Updated: January 24, 2017
Last Verified: July 25, 2011