Model-based adaptive phase I trial design of post-transplant XXXX maintenance in @entity2590 .

@entity1 @entity137 @entity2590 @entity3052 @entity11508
BACKGROUND: This report focuses on the adaptive phase I trial design aimed to find the clinically applicable dose for @entity11508 maintenance treatment after allogeneic hematopoietic stem cell transplantation in @entity1 with higher-risk @entity2590 and secondary @entity3052 . METHODS: The first cohort (three @entity1 ) was given the same initial daily dose of @entity11508 (5  mg/m(2)/day, five consecutive days with 4-week intervals). In all cohorts, the doses for Cycles 2 to 4 were individualized using pharmacokinetic-pharmacodynamic modeling and simulations. The goal of dose individualization was to determine the maximum dose for each @entity1 at which the occurrence of grade 4 (CTC-AE) @entity137 for both platelet and neutrophil counts could be avoided. The initial doses for the following cohorts were also estimated with the data from the previous cohorts in the same manner. RESULTS: In all but one @entity1 (14 out of 15), neutrophil count was the dose-limiting factor throughout the cycles. In cycles where doses were individualized, the median neutrophil nadir observed was 1100/mm(3) (grade 2) and grade 4 @entity137 occurred in 5.1  % of all cycles (while it occurred in 36.8  % where doses were not individualized). The initial doses estimated for cohorts 2 to 5 were 4, 5, 5.5, and 5  mg/m(2)/day, respectively. The median maintenance dose was 7  mg/m(2)/day. CONCLUSIONS: We determined the acceptable starting dose and individualized the maintenance dose for each @entity1 , while minimizing the @entity137 using the adaptive approach. Currently, 5  mg/m(2)/day is considered to be the most appropriate starting dose for the regimen studied. TRIAL REGISTRATION: Clinicaltrials.gov NCT01277484.
