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

ABSTRACT:

Background

This report focuses on the adaptive phase I trial design aimed to find the 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.

Methods

The first cohort (three patients) was given the same initial daily dose of decitabine (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 patient at which the occurrence of grade 4 (CTC-AE) toxicities for both platelet and neutrophil counts could be avoided. The

SUBMITTER: Han S 

PROVIDER: S-EPMC4619308 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature