Clinical Trial Simulation To Optimize Trial Design for Fludarabine Dosing Strategies in Allogeneic Hematopoietic Cell Transplantation

Jurgen B. Langenhorst, Thomas P.C. Dorlo, Charlotte van Kesteren, Erik M. van Maarseveen, Stefan Nierkens, Moniek A. de Witte, Jaap Jan Boelens, Alwin D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

3 Citaten (Scopus)

Samenvatting

Optimal fludarabine exposure has been associated with improved treatment outcome in allogeneic hematopoietic cell transplantation, 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 end point, 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 nonrelapse mortality (NRM), graft failure, or relapse, and ultimately overall survival (covering all three aforementioned outcomes). The inclusion in each treatment arm (n) required to achieve 80% power was calculated for all combinations of end points 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.

Originele taal-2Engels
Pagina's (van-tot)272-281
Aantal pagina's10
TijdschriftCPT: Pharmacometrics and Systems Pharmacology
Volume9
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 1 mei 2020

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