Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00394316
Status:
TERMINATED
Last Update Posted:
2018-07-05
First Post:
2006-10-31
Brief Title:
Gene Therapy for Chronic Granulomatous Disease
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Autologous Transplantation of Genetically Modified Cells for the Treatment of X-Linked Chronic Granulomatous Disease
Status:
TERMINATED
Status Verified Date:
2014-04-08
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:
X-linked Chronic Granulomatous Disease CGD is an inherited disorder caused by an abnormal gene that fails to make the protein known as gp91 phox This protein is part of a group of proteins that work to create hydrogen peroxide in neutrophils Neutrophils are a type of white blood cell that helps fight infections As a result patients who do not make this gp91 phox frequently develop life-threatening infections In addition these neutrophils often act abnormally resulting in the creation of a granuloma which is an abnormal collection of cells These granulomas can then become large enough to block organs such as the bladder andor intestines causing significant problems Patients are usually treated with antibiotics often needed for extended periods of time for the infections caused by CGD and with corticosteroids for the granulomas However these drugs do not cure CGD itself and can have significant side effects Thus patients with CGD do not have a normal life expectancy
The only available cure to date for CGD is Bone Marrow Transplantation BMT where the blood-making cells from a specially matched brother or sister donor allogeneic or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells If the cells from the donor engraft or survive in the marrow the patient can be cured however there is a risk that the cells may not engraft or that they may later get rejected from the body Also the cells from the donor can react against the patient causing a serious disorder called Graft Versus Host Disease GVHD Although there are a number of methods used to try to reduce andor prevent graft rejection andor GVHD these complications can still occur even with the newer methods now being developed The risks of such complications are lower when a brother or sister is used as the donor however not all patients even those with siblings will have an ideally matched donor Hence transplantation especially when using an unrelated donor is not always a perfect cure
Because the gene responsible for making the gp91 phox is known it is possible to use gene therapy to try to cure this disease In gene therapy some of the blood-making cells are taken from the patient using a technique called apheresis The normal gene is placed into the cells using special viruses called retroviruses The cells are then able to produce the normal protein In this trial the patient will receive a small dose of chemotherapy called busulfan lower than what is traditionally used in allogeneic BMT and the newly corrected cells will then be put back into the patient
Even with the best standard of care a number of patients with CGD will still die from infection For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor their only hope is either a Matched Unrelated Donor MUD transplant which has a high risk of causing death itself or gene therapy Hence we would propose using gene therapy in these patients as this has less risk of causing death but can still possibly offer a cure Even if the corrected cells do not remain life long to rid the patients entirely of their disease as long as they persist for even a few months they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol Further they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit
The only available cure to date for CGD is Bone Marrow Transplantation BMT where the blood-making cells from a specially matched brother or sister donor allogeneic or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells If the cells from the donor engraft or survive in the marrow the patient can be cured however there is a risk that the cells may not engraft or that they may later get rejected from the body Also the cells from the donor can react against the patient causing a serious disorder called Graft Versus Host Disease GVHD Although there are a number of methods used to try to reduce andor prevent graft rejection andor GVHD these complications can still occur even with the newer methods now being developed The risks of such complications are lower when a brother or sister is used as the donor however not all patients even those with siblings will have an ideally matched donor Hence transplantation especially when using an unrelated donor is not always a perfect cure
Because the gene responsible for making the gp91 phox is known it is possible to use gene therapy to try to cure this disease In gene therapy some of the blood-making cells are taken from the patient using a technique called apheresis The normal gene is placed into the cells using special viruses called retroviruses The cells are then able to produce the normal protein In this trial the patient will receive a small dose of chemotherapy called busulfan lower than what is traditionally used in allogeneic BMT and the newly corrected cells will then be put back into the patient
Even with the best standard of care a number of patients with CGD will still die from infection For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor their only hope is either a Matched Unrelated Donor MUD transplant which has a high risk of causing death itself or gene therapy Hence we would propose using gene therapy in these patients as this has less risk of causing death but can still possibly offer a cure Even if the corrected cells do not remain life long to rid the patients entirely of their disease as long as they persist for even a few months they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol Further they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit
Detailed Description:
X-linked Chronic Granulomatous Disease CGD is an inherited disorder caused by an abnormal gene that fails to make the protein known as gp91 phox This protein is part of a group of proteins that work to create hydrogen peroxide in neutrophils Neutrophils are a type of white blood cell that helps fight infections As a result patients who do not make this gp91 phox frequently develop life-threatening infections In addition these neutrophils often act abnormally resulting in the creation of a granuloma which is an abnormal collection of cells These granulomas can then become large enough to block organs such as the bladder andor intestines causing significant problems Patients are usually treated with antibiotics often needed for extended periods of time for the infections caused by CGD and with corticosteroids for the granulomas However these drugs do not cure CGD itself and can have significant side effects Thus patients with CGD do not have a normal life expectancy
The only available cure to date for CGD is Bone Marrow Transplantation BMT where the blood-making cells from a specially matched brother or sister donor allogeneic or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells If the cells from the donor engraft or survive in the marrow the patient can be cured however there is a risk that the cells may not engraft or that they may later get rejected from the body Also the cells from the donor can react against the patient causing a serious disorder called Graft Versus Host Disease GVHD Although there are a number of methods used to try to reduce andor prevent graft rejection andor GVHD these complications can still occur even with the newer methods now being developed The risks of such complications are lower when a brother or sister is used as the donor however not all patients even those with siblings will have an ideally matched donor Hence transplantation especially when using an unrelated donor is not always a perfect cure
Because the gene responsible for making the gp91 phox is known it is possible to use gene therapy to try to cure this disease In gene therapy some of the blood-making cells are taken from the patient using a technique called apheresis The normal gene is placed into the cells using special viruses called retroviruses The cells are then able to produce the normal protein In this trial the patient will receive a small dose of chemotherapy called busulfan lower than what is traditionally used in allogeneic BMT Then the newly corrected cells will be put back into the patient
Even with the best standard of care a number of patients with CGD will still die from infection For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor their only hope is either a Matched Unrelated Donor MUD transplant which has a high risk of causing death itself or gene therapy Hence we would propose using gene therapy in these patients as this has less risk of causing death but can still possibly offer a cure Even if the corrected cells do not remain lifelong to rid the patients entirely of their disease as long as they persist for even a few months they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol Further they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit
The only available cure to date for CGD is Bone Marrow Transplantation BMT where the blood-making cells from a specially matched brother or sister donor allogeneic or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells If the cells from the donor engraft or survive in the marrow the patient can be cured however there is a risk that the cells may not engraft or that they may later get rejected from the body Also the cells from the donor can react against the patient causing a serious disorder called Graft Versus Host Disease GVHD Although there are a number of methods used to try to reduce andor prevent graft rejection andor GVHD these complications can still occur even with the newer methods now being developed The risks of such complications are lower when a brother or sister is used as the donor however not all patients even those with siblings will have an ideally matched donor Hence transplantation especially when using an unrelated donor is not always a perfect cure
Because the gene responsible for making the gp91 phox is known it is possible to use gene therapy to try to cure this disease In gene therapy some of the blood-making cells are taken from the patient using a technique called apheresis The normal gene is placed into the cells using special viruses called retroviruses The cells are then able to produce the normal protein In this trial the patient will receive a small dose of chemotherapy called busulfan lower than what is traditionally used in allogeneic BMT Then the newly corrected cells will be put back into the patient
Even with the best standard of care a number of patients with CGD will still die from infection For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor their only hope is either a Matched Unrelated Donor MUD transplant which has a high risk of causing death itself or gene therapy Hence we would propose using gene therapy in these patients as this has less risk of causing death but can still possibly offer a cure Even if the corrected cells do not remain lifelong to rid the patients entirely of their disease as long as they persist for even a few months they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol Further they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit
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 |
|---|---|---|---|
| 07-I-0017 | None | None | None |