Granulomatous DiseasePhase 1NCT00092937
Use of Busulfan as Conditioning Agent for a Second Stem Cell Transplant
A Phase 1 study testing Busulfan in people with Granulomatous Disease and Chronic, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Granulomatous Disease, Chronic
- What is being tested?
- Busulfan
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2004to 6 Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
- RECIPIENT INCLUSION/EXCLUSION CRITERIA:
- The recipient fulfills by study design the inclusion criteria
- The patient however, would be considered ineligible for the study only If his donor is unable to participate.
DONOR EXCLUSION CRITERIA:
- Pregnant or lactating.
- Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).
- HIV positive.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient With Partial Reconstitution Post Initial Allogeneic Transplantation
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 patient's 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 patient's own cells. This is good if it is against abnormal cells, but bad if serious damage occurs to the patient's vital organs. GVHD is treated with steroids and cyclosporine, and possibly other drugs if needed.
Read the 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 patient's myeloid engraftment so as to ostensibly cure him of his CGD.
- Conditions
- Granulomatous Disease, Chronic
- Being tested
- Busulfan
- Keywords
- Chronic Granulomatous Disease, Nonmyeloablative, CD34 Positive Cells, Donor Engraftment, Myeloid Chimerism
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2004 (estimated)
- Study start23 Sep 2004
- Primary completion6 Apr 2010
- Study completion6 Apr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00092937
- Sponsor's protocol ID
- 040289
- Other IDs
- 04-I-0289
- Status last verified
- 6 Apr 2010
- First submitted
- 24 Sep 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69. doi: 10.1097/00005792-200005000-00003.
PubMed 10844935Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan;8(1):17-22. doi: 10.1097/00062752-200101000-00004.
PubMed 11138621Roesler J, Brenner S, Bukovsky AA, Whiting-Theobald N, Dull T, Kelly M, Civin CI, Malech HL. Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. Blood. 2002 Dec 15;100(13):4381-90. doi: 10.1182/blood-2001-12-0165. Epub 2002 Aug 1.
PubMed 12393624
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient With Partial Reconstitution Post Initial Allogeneic Transplantation
- ClinicalTrials.gov ID
- NCT00092937
- Acronym / sponsor ID
- 040289
- Conditions
- Granulomatous Disease, Chronic
- Keywords
- Chronic Granulomatous Disease, Nonmyeloablative, CD34 Positive Cells, Donor Engraftment, Myeloid Chimerism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 23 Sep 2004
- Primary completion
- 6 Apr 2010 (actual)
- Study completion
- 6 Apr 2010 (actual)
- First posted
- 27 Sep 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 patient's 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 patient's own cells. This is good if it is against abnormal cells, but bad if serious damage occurs to the patient's 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 patient's myeloid engraftment so as to ostensibly cure him of his CGD.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Busulfan | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10844935Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69. doi: 10.1097/00005792-200005000-00003.
- Background: PubMed 11138621Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan;8(1):17-22. doi: 10.1097/00062752-200101000-00004.
- Background: PubMed 12393624Roesler J, Brenner S, Bukovsky AA, Whiting-Theobald N, Dull T, Kelly M, Civin CI, Malech HL. Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. Blood. 2002 Dec 15;100(13):4381-90. doi: 10.1182/blood-2001-12-0165. Epub 2002 Aug 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Busulfan in people with Granulomatous Disease and Chronic, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00092937, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.