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

Phase 4 Completed 72 enrolled H. Lee Moffitt Cancer Center and Research Institute

Non-randomizedSingle-groupOpen-labelTreatment

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.

Timeline

Start: 2005-08
Primary completion: 2012-02
Completion: 2012-02

Outcome

Missed primary endpoint

registry AUC 6000 vs AUC 7500 vs AUC 9000; p = .07; Hazard Ratio (HR) 6.27 (95% CI 0.92 to 42.48); Gray NCT00361140 ↗

Publications

Results Perkins JB, Kim J, Anasetti C, Fernandez HF, Perez LE, Ayala E, Kharfan-Dabaja MA, Tomblyn MR, Sullivan DM, Pidala JA, Field TL. Maximally tolerated busulfan systemic exposure in combination with fludarabine as conditioning before allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012 Jul;18(7):1099-107. doi: 10.1016/j.bbmt.2011.12.584. Epub 2011 Dec 23.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Busulfan	Small molecule	170 mg/m2	Intravenous
Subject	Busulfan	Small molecule	180 mg/m2	Intravenous
Subject	Busulfan	Small molecule	220 mg/m2	Intravenous
Background	Fludarabine	Small molecule	40 mg/m2	Intravenous