Use of Busulfan as Conditioning Agent for a Second Stem Cell Transplant

NCT00092937 | Completed Phase 1

• 2 other identifiers: 04028904-I-0289
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Granulomatous Disease; Chronic

Keywords

Chronic Granulomatous Disease; Nonmyeloablative; CD34 Positive Cells; Donor Engraftment; Myeloid Chimerism

Interventions

Busulfan DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• The patient however, would be considered ineligible for the study only If his donor is unable to participate.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 10844935 BACKGROUND

• Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan;8(1):17-22. doi: 10.1097/00062752-200101000-00004.

  PMID: 11138621 BACKGROUND

• Roesler 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.

  PMID: 12393624 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Granulomatous Disease, Chronic

Interventions

Busulfan

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 24, 2004
• First Posted: September 27, 2004
• Study Start: September 23, 2004
• Primary Completion: April 6, 2010
• Study Completion: April 6, 2010
• Last Updated: July 2, 2017

Record last verified: 2010-04-06

Locations

US (1)