Ignite Creation Date:
2024-05-06 @ 5:53 PM
Last Modification Date:
2024-10-26 @ 2:37 PM
Study NCT ID:
NCT05463133
Status:
RECRUITING
Last Update Posted:
2024-07-05
First Post:
2022-07-15
Brief Title:
Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease CGD With an Alemtuzumab Busulfan and TBI-based Conditioning Regimen Combined With Cytokine IL-6 - IFN-gamma Antagonists
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase III Study Using Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease With an Alemtuzumab Busulfan and TBI-based Conditioning Regimen Combined With Cytokine IL-6 - IFN-gamma Antagonists
Status:
RECRUITING
Status Verified Date:
2024-10-16
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:
Background
Chronic granulomatous disease CGD affects the immune system People with CGD are more likely to get infections Drugs can help control infections but these treatments can cause side effects including kidney failure and deafness Stem cell transplants can cure CGD but these don t always work
Objective
To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD
Eligibility
People aged 4-65 years with CGD
Design
Participants will undergo screening They will have a physical exam They will have blood and urine tests and tests of their heart function and breathing They will have imaging scans They will have a bone marrow biopsy a needle will be inserted into their hip to draw a sample of tissue from the bone
A tube called a catheter will be placed into a vein in the participant s chest This catheter will remain in place for the transplant and recovery period Blood for tests can be drawn from the catheter and medications and the stem cells can be administered through it
Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant They will get 2 doses of total body radiation on the same day
Participants will receive donor stem cells through the catheter They will remain in the hospital for 6 weeks afterward
Participants will visit the clinic 2 to 3 times per week for 3 months after discharge
Follow-up visits will continue for 5 years
Chronic granulomatous disease CGD affects the immune system People with CGD are more likely to get infections Drugs can help control infections but these treatments can cause side effects including kidney failure and deafness Stem cell transplants can cure CGD but these don t always work
Objective
To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD
Eligibility
People aged 4-65 years with CGD
Design
Participants will undergo screening They will have a physical exam They will have blood and urine tests and tests of their heart function and breathing They will have imaging scans They will have a bone marrow biopsy a needle will be inserted into their hip to draw a sample of tissue from the bone
A tube called a catheter will be placed into a vein in the participant s chest This catheter will remain in place for the transplant and recovery period Blood for tests can be drawn from the catheter and medications and the stem cells can be administered through it
Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant They will get 2 doses of total body radiation on the same day
Participants will receive donor stem cells through the catheter They will remain in the hospital for 6 weeks afterward
Participants will visit the clinic 2 to 3 times per week for 3 months after discharge
Follow-up visits will continue for 5 years
Detailed Description:
Chronic Granulomatous Disease CGD is an inherited disorder resulting from a failure to produce nicotinamide adenine dinucleotide phosphate NADPH oxidase necessary for protection against a number of infectious organisms Patients are subject to recurrent infections and inflammatory complications The current management of these patients is limited to close surveillance for infections administration of prophylactic antimicrobials and rapid and aggressive treatment of suspected and documented infections with broad-spectrum antibiotics Although often effective these treatments can require long hospitalizations impacting the overall quality of life significantly and leading to significant morbidity such as renal failure and deafness CGD patients have autoinflammation that may manifest as inflammatory bowel disease hypoxic lung inflammation andor liver nodular regenerative hyperplasia with venopathy as examples
Currently the only available cure for these disorders is bone marrow transplantation which preferentially uses a human leukocyte antigen HLA-matched related sibling as the donor allogeneic stem cell transplantation However as only 30 of participants in the general population have an HLA-matched related sibling allogeneic related transplantation is often not an option resulting in the need for matched unrelated donor MUD transplantation The National Marrow Donor Program NMDP serves as both a national registry of volunteers who are willing to donate progenitor cells to eligible recipients as well as a repository of cord blood products Despite continued improvement in the use of transplantation schemas- including the development of nonmyeloablative regimens-there remain significant morbidity and mortality associated with transplantation in particular graft versus host disease GvHD and graft rejection CGD with severe autoinflammation manifested as C-reactive protein CRP 100 milligrams per milliliter mgmL has been a significant risk factor for mortality due to severe engraftment syndrome and thus patients with elevated CRPs have not been eligible for prior transplant protocols
In addition despite improving engraftment rates there continues to be mixed chimerism and late graft loss in CGD participants despite a variety of conditioning regimens being used at various centers
In our most recent protocol we have continued to have a low incidence of graft versus host disease and improved engraftment but still could see improvement in graft stability Thus in order to improve outcomes with participants with elevated CRPs as well as improve overall engraftment we are building on our prior regimens by targeting the inflammatory cytokines that appear to be involved in graft failure and engraftment syndrome
Participants with a CRP of less than 100 mgmL will be pretreated with a dose of tocilizumab an anti-IL6 monoclonal antibody Participants with a CRP of greater than 100 mgmL will be pretreated with 2 doses of tocilizumab as well as an inhibitor of interferon-gamma in order to decrease the inflammation that has been seen in these participants with engraftment Otherwise the conditioning regimen will be similar to maintain the low rates of GvHD that we have seen to date
Currently the only available cure for these disorders is bone marrow transplantation which preferentially uses a human leukocyte antigen HLA-matched related sibling as the donor allogeneic stem cell transplantation However as only 30 of participants in the general population have an HLA-matched related sibling allogeneic related transplantation is often not an option resulting in the need for matched unrelated donor MUD transplantation The National Marrow Donor Program NMDP serves as both a national registry of volunteers who are willing to donate progenitor cells to eligible recipients as well as a repository of cord blood products Despite continued improvement in the use of transplantation schemas- including the development of nonmyeloablative regimens-there remain significant morbidity and mortality associated with transplantation in particular graft versus host disease GvHD and graft rejection CGD with severe autoinflammation manifested as C-reactive protein CRP 100 milligrams per milliliter mgmL has been a significant risk factor for mortality due to severe engraftment syndrome and thus patients with elevated CRPs have not been eligible for prior transplant protocols
In addition despite improving engraftment rates there continues to be mixed chimerism and late graft loss in CGD participants despite a variety of conditioning regimens being used at various centers
In our most recent protocol we have continued to have a low incidence of graft versus host disease and improved engraftment but still could see improvement in graft stability Thus in order to improve outcomes with participants with elevated CRPs as well as improve overall engraftment we are building on our prior regimens by targeting the inflammatory cytokines that appear to be involved in graft failure and engraftment syndrome
Participants with a CRP of less than 100 mgmL will be pretreated with a dose of tocilizumab an anti-IL6 monoclonal antibody Participants with a CRP of greater than 100 mgmL will be pretreated with 2 doses of tocilizumab as well as an inhibitor of interferon-gamma in order to decrease the inflammation that has been seen in these participants with engraftment Otherwise the conditioning regimen will be similar to maintain the low rates of GvHD that we have seen to date
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| 000977-I | None | None | None |