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Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00092937 |
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:
Condition | Intervention | Phase |
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Granulomatous Disease Chronic |
Drug: Busulfan |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient With Partial Reconstitution Post Initial Allogeneic Transplantation |
Estimated Enrollment: | 2 |
Study Start Date: | September 2004 |
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.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
DONOR EXCLUSION CRITERIA:
Study ID Numbers: | 040289, 04-I-0289 |
Study First Received: | September 24, 2004 |
Last Updated: | July 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00092937 |
Health Authority: | United States: Federal Government |
Chronic Granulomatous Disease Nonmyeloablative CD34 Positive Cells Donor Engraftment Myeloid Chimerism |
Lymphatic Diseases Busulfan Granulomatous Disease, Chronic Neoplasm Metastasis |
Chronic granulomatous disease Lymphoproliferative Disorders Granuloma |
Pathologic Processes Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Therapeutic Uses Physiological Effects of Drugs |
Myeloablative Agonists Antineoplastic Agents, Alkylating Alkylating Agents Immunosuppressive Agents Pharmacologic Actions |