Study design
POLAND
A prospective, randomized (1:1), open-label, multicenter, active-controlled, parallel-group phase 2 clinical trial (MC-FludT.16/NM) was conducted across 4 European countries between April 2015 to June 2021. Each treatment arm also administered fludarabine whereas thiotepa could be added for intensification of the regimen at the treating physicians’ discretion before randomization. Pharmacokinetic analyses on treosulfan were conducted to contribute to a final population pharmacokinetics (Pop-PK) model. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and the applicable national laws of the participating countries (Czech Republic, Germany, Italy, Poland). All patients and/or their parents/legal guardians provided written consent prior to the participation in the study.Randomization (1:1 ratio using a permuted block technique) for either treosulfan or busulfan was performed centrally by the sponsor’s clinical research department using a computer-generated randomization list and was stratified by the 2 regimens. Treosulfan was administered IV over 2 hours consecutively on Day -6, -5, and -4. Based on an initially evaluated Pop-PK model, the individual total dose of treosulfan was adapted on the actual body surface area (BSA) [Further information for actual administration of the preparative regimens is provided (Supplementary Section 