Randomized Phase III Comparison of 12 Gy TBI and Cyclophosphamide 120 mg/kg With Fludarabine 120 mg/Sqm and 8 Gy TBI Before Allogeneic Transplantation in Patients With Acute Myeloid Leukemia in First Remission
Transplant-related deaths because of extramedullary toxicity and graft-versus host disease
remain the major causes for treatment-failure in patients with AMl receiving allogeneic
hematopoietic stem cell transplantation.
In phase II study, M . Stelljes and coworkers could show, that a reduced dose of total-body-
irradiation and fludarabine can be safely used in patients with AML at various disease
stages. The best results could be achieved in patients who had been in complete remission by
the time of inclusion.
Therefore this prospective trial was initiated to compare the new conditioning regimen with
the standard regimen of 12 Gy TBI/Cyclophosphamide 120 mg/kg in patients ith AML in first
After having achieved complete remission, and giving informed consent, patients are
stratified according to marrow cytogenetics, age and type of induction therapy and
subsequently randomized to receive on of the mentioned conditioning therapies.
The primary end-point will be non-relapse mortality. The hypothesis would be, that the
one-year mortality can be reduced from 25 to 15%. Given a power of 0.8 and a first-error of
5%, 252 patients will have to be randomized.
Secondary endpoints include:
3 year overall-and disease-free survival Rate of grade II-IV acute GvHD Rate of grade 3-4
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Treatment-related mortality at 12 months after transplantation
Proportion of patients dying without prior relapse
Gerhard Ehninger, MD
Director of Med. Klink und Poliklinik I, Technical University Dresden
Germany: Federal Institute for Drugs and Medical Devices