Optimal fludarabine exposure has been associated with improved treatment outcome in allogeneic hematopoietic cell transplantation (HCT), suggesting potential benefit of individualized dosing. A randomized controlled trial (RCT) comparing alternative fludarabine dosing strategies to current practice may be warranted, but should be sufficiently powered for a relevant endpoint, while still feasible to enroll. To find the optimal design, we simulated RCTs comparing current practice (160 mg/m2 ) to either covariate-based or therapeutic drug monitoring (TDM)-guided-dosing with potential outcomes being non-relapse mortality (NRM), graft failure, or relapse, and ultimately overall survival (OS, covering all three aforementioned outcomes). The inclusion in each treatment arm (n) required to achieve 80% power was calculated for all combinations of endpoints and dosing comparisons. The trial requiring the lowest n for sufficient power compared TDM-guided-dosing to current practice with NRM as primary outcome (n=70, NRM decreasing from 21% to 5.7%). We conclude that a superiority trial is feasible.