Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00028236
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-12-17
Brief Title:
Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency XSCID
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Ex Vivo Retroviral Gene Transfer For Treatment of X-Linked Severe Combined Immunodeficiency XSCID
Status:
COMPLETED
Status Verified Date:
2011-07-25
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 andor 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 15-20 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 patients 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 effects from the chemotherapy and possibly try to improve the development of the T cells 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 transduction of HSC from post-BMT XSCID subjects 2 administration of a nonmyeloablative conditioning regimen in older patients to improve engraftment 3 administration of a transduced HSC to eight subjects 4 administration of KGF to improve thymic function post transplant to improve T cell development and 5 appropriate follow-up of the treated subjects to monitor vector sequence distribution gc expression in hematopoietic lineages and lymphoctye numbers and function as well as general health and immune status
Detailed Description:
This is a Phase III 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 andor 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 15-20 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 10 x 106 CD34 HSCkg 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 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 ngmL Flt3-L 50 ngmL SCF 50 ngmL TPO 25 ngmL IL-6 and 5 ngmL IL-3 Subjects who are older than the age of 3 will be given a conditioning regimen consisting of Fludarabine and Busulfan then they will receive a single infusion of transduced HSC Prior to the chemotherapy and following the infusion of the cells the same patients will also be given Keratinocyte growth factor KGF also known as palifermin 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 a nonmyeloablative conditioning regimen to improve engraftment 3 administration of transduced HSC to eight subjects 4 administration of KGF to improve thymic function post transplant to improve T cell development and 5 appropriate 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
We will enroll eight older XSCID patients 15-20 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 10 x 106 CD34 HSCkg 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 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 ngmL Flt3-L 50 ngmL SCF 50 ngmL TPO 25 ngmL IL-6 and 5 ngmL IL-3 Subjects who are older than the age of 3 will be given a conditioning regimen consisting of Fludarabine and Busulfan then they will receive a single infusion of transduced HSC Prior to the chemotherapy and following the infusion of the cells the same patients will also be given Keratinocyte growth factor KGF also known as palifermin 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 a nonmyeloablative conditioning regimen to improve engraftment 3 administration of transduced HSC to eight subjects 4 administration of KGF to improve thymic function post transplant to improve T cell development and 5 appropriate 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-I-0057 | None | None | None |