Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard Conditioning Regimens
To compare efficacy and safety of Treosulfan-based conditioning (test) with i.v.
Busulfan-based reduced intensity conditioning (reference).
The statistical aim of the study is to show non-inferiority with respect to:
Event-free survival (EFS) within 1 year after transplantation. Events are defined as relapse
of disease, graft failure or death (whatever occurs first).
1. Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between
day -6 and day +28
2. Comparative evaluation of overall survival (OS) and cumulative incidence of relapse
(RI) as well as non-relapse mortality (NRM) and transplantation-related mortality (TRM)
3. Comparative evaluation of day +28 conditional cumulative incidence of engraftment
4. Comparative evaluation of day +28 and day +100 incidence of complete donor-type
5. Comparative evaluation of cumulative incidence of acute and chronic GvHD
6. Comparative evaluation of incidence of other CTC grade III/IV adverse events between
day -6 and day +28
Individual patients will be followed-up for at most 1 year after transplantation. Three
confirmatory interim evaluations and one final analysis are planned, which allow to stop the
trial as soon as the question of non-inferiority is answered (as outlined below). In
addition, post-surveillance with respect to OS and EFS will be conducted one year after
inclusion of the last study patient.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival (EFS)
within 1 year after transplantation
Dietrich W. Beelen, MD
University Hospital, Essen
Germany: Federal Institute for Drugs and Medical Devices