NCT00361140

Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)

Busulfan Dose Escalation Study Based on AUC in the Setting of Busulfan/Fludarabine Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation (HCT)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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 area under the plasma concentration time curve (AUC). Day 0 is the day of hematopoietic progenitor cell reinfusion. Supportive care will be based on institutional guidelines. Blood samples will be collected for dose modification based on the AUC levels. Dose escalation will proceed to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Detailed description

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 post-transplant.

Conditions

• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Leukemia, Lymphocytic
• Myeloma
• Lymphoma

Interventions

Type	Name	Description
DRUG	Busulfan	Bu IV (BusulfexR) over 3 hours on days -6, -5, -4, and -3. Day -6 and -5 doses for patients on Level 1 will be 170mg/m2. This dose is based on the dose used by DeLima (2004) adjusted proportionately to achieve an AUC of 6000uM-min. Subsequent daily doses for patients on Level 1 will be adjusted to achieve an average AUC of 6000uM-min. Day -6 and -5 doses for patients on Level 2 will be based on the mean dose required on Level 1 to achieve target AUC then adjusted proportionally for new target AUC. Subsequent daily doses will be adjusted to achieve target AUCs.
DRUG	Fludarabine	Fludarabine 40mg/m2 IV over 1 hour on days -6, -5, -4, and -3

Timeline

• Start date: 2005-08-01
• Primary completion: 2012-02-01
• Completion: 2012-02-01
• First posted: 2006-08-07
• Last updated: 2017-03-03
• Results posted: 2013-06-27

Locations

1 site across 1 country: United States