Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00092937
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2004-09-24
Brief Title:
Use of Busulfan as Conditioning Agent for a Second Stem Cell Transplant
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient With Partial Reconstitution Post Initial Allogeneic Transplantation
Status:
COMPLETED
Status Verified Date:
2010-04-06
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 protocol is designed for a single specific patient It uses busulfan as a conditioning agent in a second stem cell transplant procedure for a patient with chronic granulomatous disease CGD a disorder in which a certain type of white cells called myeloid cells do not function properly This causes increased risk of serious bacterial and fungal infections that can lead to organ dysfunction such as kidney disease as well as formation of granulomas-non-cancerous masses that can cause obstructions in the esophagus stomach and intestines and block urine flow from the kidneys and bladder The child in this study has previously undergone a stem cell transplant to treat CGD and as a result he is now producing normal lymphocytes another type of white cell However the myeloid cells from the donor did not engraft successfully and the patient is still producing his own defective myeloid cells In this study the child will undergo a second stem cell transplant in combination with busulfan a drug that targets myeloid cells killing them to make way for healthy donated myeloid cells
Treatment includes the following procedures
Medical evaluation to confirm that the patient is healthy enough to undergo the transplantation
Treatment with busulfan injected through the patients central venous line
Stem cell transplantation through the central venous line
Blood tests on days 25 56 and 91 after the transplant to assess how many cells are of donor origin
Bone marrow aspiration on day 100 and then at 12 24 and 36 months to assess how many cells are of donor origin
Pulmonary function breathing test at 12 and 24 months
Physical examination and blood tests weekly or twice weekly for the first 2 to 3 months and at 4 6 12 18 24 36 48 and 60 months after transplant
Treatment for graft-versus-host disease GVHD if this complication develops GVHD is the attack of lymphocytes from the donor against the patients own cells This is good if it is against abnormal cells but bad if serious damage occurs to the patients vital organs GVHD is treated with steroids and cyclosporine and possibly other drugs if needed
Treatment includes the following procedures
Medical evaluation to confirm that the patient is healthy enough to undergo the transplantation
Treatment with busulfan injected through the patients central venous line
Stem cell transplantation through the central venous line
Blood tests on days 25 56 and 91 after the transplant to assess how many cells are of donor origin
Bone marrow aspiration on day 100 and then at 12 24 and 36 months to assess how many cells are of donor origin
Pulmonary function breathing test at 12 and 24 months
Physical examination and blood tests weekly or twice weekly for the first 2 to 3 months and at 4 6 12 18 24 36 48 and 60 months after transplant
Treatment for graft-versus-host disease GVHD if this complication develops GVHD is the attack of lymphocytes from the donor against the patients own cells This is good if it is against abnormal cells but bad if serious damage occurs to the patients vital organs GVHD is treated with steroids and cyclosporine and possibly other drugs if needed
Detailed Description:
This is a single patient study using intravenous busulfan as a conditioning agent for a second allogeneic stem cell transplant in order to increase myeloid engraftment in a previously transplanted recipient with chronic granulomatous disease CGD
CGD is an inherited disorder of neutrophil function leading to increased risk of infections from both common and rare microorganisms including fungi Although these infections can often be prevented or successfully treated there are long-term sequelae including organ dysfunction as a result of both the infections and the treatment For example many of the anti-fungal agents cause renal impairment and can even lead to kidney failure requiring dialysis In addition the abnormal functioning of the neutrophils leads to the development of granulomas which can cause obstruction of various organs in particular within the gastrointestinal and urogenital systems with sometimes serious sequelae As a result the life expectancy of patients with CGD is significantly limited with no patients documented reaching the age of 50 and a 2 percent mortality rate per year of life
Currently the only available cure of CGD is bone marrow transplantation however given its own inherent associated morbidities and mortality as well as the necessity for a matched related donor this has not been offered to all patients More recently attempts to reduce the toxicities of this potentially curative treatment have lead to the development of non-myeloablative regimens which as a result can lead to partial engraftment of the donor cells into the recipient a situation referred to as mixed chimerism In order to achieve an adequate number of normal neutrophils for clinical benefit the level of donor chimerism needs to be at least 5 percent in the myeloid lineage One of the patients treated on a previous protocol with a novel nonmyeloablative conditioning regimen has had 100 percent engraftment of his lymphoid cells but less than 1percent engraftment of his myeloid lineage As a result he continues to experience the problems associated with CGD but has had no problems of graft versus host disease GVHD In order to improve his myeloid engraftment while taking advantage of the presence of his 100 percent lymphoid chimerism we propose to treat him with moderate dose busulfan and a purified stem cell product from the original donor as a second transplant With this study the goal will be to improve this patients myeloid engraftment so as to ostensibly cure him of his CGD
CGD is an inherited disorder of neutrophil function leading to increased risk of infections from both common and rare microorganisms including fungi Although these infections can often be prevented or successfully treated there are long-term sequelae including organ dysfunction as a result of both the infections and the treatment For example many of the anti-fungal agents cause renal impairment and can even lead to kidney failure requiring dialysis In addition the abnormal functioning of the neutrophils leads to the development of granulomas which can cause obstruction of various organs in particular within the gastrointestinal and urogenital systems with sometimes serious sequelae As a result the life expectancy of patients with CGD is significantly limited with no patients documented reaching the age of 50 and a 2 percent mortality rate per year of life
Currently the only available cure of CGD is bone marrow transplantation however given its own inherent associated morbidities and mortality as well as the necessity for a matched related donor this has not been offered to all patients More recently attempts to reduce the toxicities of this potentially curative treatment have lead to the development of non-myeloablative regimens which as a result can lead to partial engraftment of the donor cells into the recipient a situation referred to as mixed chimerism In order to achieve an adequate number of normal neutrophils for clinical benefit the level of donor chimerism needs to be at least 5 percent in the myeloid lineage One of the patients treated on a previous protocol with a novel nonmyeloablative conditioning regimen has had 100 percent engraftment of his lymphoid cells but less than 1percent engraftment of his myeloid lineage As a result he continues to experience the problems associated with CGD but has had no problems of graft versus host disease GVHD In order to improve his myeloid engraftment while taking advantage of the presence of his 100 percent lymphoid chimerism we propose to treat him with moderate dose busulfan and a purified stem cell product from the original donor as a second transplant With this study the goal will be to improve this patients myeloid engraftment so as to ostensibly cure him of his CGD
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 |
|---|---|---|---|
| 04-I-0289 | None | None | None |