Busulfan Dose Escalation Study Based on AUC in the Setting of Busulfan/Fludarabine Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation (HCT)
Patients will receive anti-seizure prophylaxis beginning on day -7. Pre-transplant
conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and
-3. Daily treatment doses will be adjusted to achieve target AUCs (area under the plasma
concentration time curve). Day 0 is the day of hematopoietic progenitor cell reinfusion.
Supportive care will be based on institutional guidelines. In an effort to prevent
hepatotoxicity, ursodiol will be given to patients. During chemotherapy patients will not
receive concurrent metronidazole, itraconazole, or be given acetaminophen.
Blood samples will be collected at specific times after Dose 1 and Dose 4 and dose
modification will be determined or based on the desired AUC levels. Doses 3 and/or 4 will
be adjusted to achieve an average daily Busulfan AUC over the 4 treatment days.
Dose escalation will proceed through 3 dose levels to determine the maximally tolerated
level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.
Graft assessment, processing, and characterization will be done as per institutional
guidelines. Donor-recipient chimerism (two genetically distinct types of blood cells) will
be characterized by samples obtained pre-transplant and on days 30+/- 7, 90+/-7 and 360+/-30
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The number of subjects dead due to causes unrelated to relapse within the first 100 days post transplant
Teresa Field, PhD, MD
H. Lee Moffitt Cancer Center and Research Institute
United States: Institutional Review Board
|H. Lee Moffitt Cancer Center & Research Institute||Tampa, Florida 33612|