Model-based adaptive phase I trial design of post-transplant decitabine maintenance in myelodysplastic syndrome

• DOI: 10.1186/s13045-015-0208-3
• Publication Date: 2015-10-24T13:40:42Z
• Authors: Seunghoon Han; Yoo-Jin Kim; Jongtae Lee; Sangil Jeon; Taegon Hong; Gab-jin Park; Jae-Ho Yoon; Seung-Ah Yahng; Seung-Hwan Shin; Sung-Eun Lee; Ki-Seong Eom; Hee-Je Kim; Chang-Ki Min; Seok Lee; Dong-Seok Yim
• Keywords: Decitabine; Pharmacodynamics; Absolute neutrophil count

This report focuses on the adaptive phase I trial design aimed to find clinically applicable dose for decitabine maintenance treatment after allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome and secondary acute myeloid leukemia. The first cohort (three patients) was given same initial daily of (5 mg/m2/day, five consecutive days 4-week intervals). In all cohorts, doses Cycles 2 4 were individualized using pharmacokinetic-pharmacodynamic modeling simulations. goal individualization determine maximum each patient at which occurrence grade (CTC-AE) toxicities both platelet neutrophil counts could be avoided. following cohorts also estimated data from previous manner. but one (14 out 15), count dose-limiting factor throughout cycles. cycles where individualized, median nadir observed 1100/mm3 (grade 2) toxicity occurred 5.1 % (while it 36.8 not individualized). 5 4, 5, 5.5, respectively. 7 mg/m2/day. We determined acceptable starting patient, while minimizing approach. Currently, mg/m2/day is considered most appropriate regimen studied. Clinicaltrials.gov NCT01277484