NCT00822393

Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 570 (actual)
• Sponsor: medac GmbH · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. The protocol is based on results of previous phase I/II trials evaluating Treosulfan/Fludarabine conditioning prior to allogeneic haematopoietic stem cell transplantation. The reference arm (reduced intensity i.v. Busulfan/Fludarabine) is considered to be accepted medical practice for the study patient population.

Detailed description

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 2 years 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)within 2 years after transplantation 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 chimerism 5. Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation 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 2 years 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 transplantation of the last randomised patient.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Busulfan	4 x 0.8 mg/kg/d Intravenous Day -4 and -3
DRUG	Treosulfan	10 g/m2/d Intravenous Day -4, -3, -2

Timeline

• Start date: 2008-11-24
• Primary completion: 2018-01-25
• Completion: 2018-01-25
• First posted: 2009-01-14
• Last updated: 2020-07-30

Locations

33 sites across 6 countries: Finland, France, Germany, Hungary, Italy, Poland