A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia
- Determine the best dose of treosulfan when administered with fludarabine as a
reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell
transplantation, in terms of incidence of severe to fatal toxicity to major organ
systems and incidence of graft failure, in patients with acute myeloid leukemia,
lymphoblastic leukemia, or myelodysplastic syndrome.
- Determine the safety of this regimen, in terms of incidence of grade II-IV acute and
chronic graft-versus-host disease, in these patients.
- Determine, preliminarily, the efficacy of this regimen, in terms of incidence of
relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and
incidence of 200-day and 1-year nonrelapse mortality, in these patients.
- Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients
treated with this regimen.
OUTLINE: This is a multicenter, dose-finding study of treosulfan.
- Reduced-intensity conditioning: Patients receive treosulfan IV over 2 hours on days -6
to -4 and fludarabine IV over 30 minutes on days -6 to -2.
Cohorts of 5-10 patients receive escalating/de-escalating doses of treosulfan until the best
dose is determined among the 3 pre-selected doses. The best dose is defined as the dose
preceding that at which 4 of 10 patients experience dose-limiting toxicity.
- Allogeneic hematopoietic cell transplantation (AHCT): Patients undergo allogeneic bone
marrow or peripheral blood stem cell transplantation on day 0.
All male patients with acute lymphoblastic leukemia OR male patients with acute myeloid
leukemia who have prior or current testicular involvement receive external-beam radiotherapy
to the testicles before AHCT.
After completion of study treatment, patents are followed periodically.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal
34 days and 2 years
Eneida Nemecek, MD
OHSU Knight Cancer Institute
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|
|OHSU Knight Cancer Institute||Portland, Oregon 97239|