A Phase III Randomized Study Comparing Busulfan-Total Body Irradiation Versus Cyclophosphamide-Total Body Irradiation Preparative Regimen in Patients With Advanced Myelodysplastic Syndrome (MDS) or MDS-Related Acute Myeloid Leukemia (AML) Undergoing HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation, (A BMT Study)

Trial Information

A Phase III Randomized Study Comparing Busulfan-Total Body Irradiation Versus Cyclophosphamide-Total Body Irradiation Preparative Regimen in Patients With Advanced Myelodysplastic Syndrome (MDS) or MDS-Related Acute Myeloid Leukemia (AML) Undergoing HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation, (A BMT Study)

OBJECTIVES: I. Compare event free survival after total body irradiation (TBI) plus busulfan
versus TBI plus cyclophosphamide followed by allogeneic peripheral blood stem cell
transplantation in patients with advanced myelodysplastic syndrome (MDS) or MDS related
acute myeloid leukemia. II. Determine the distribution of pharmacokinetic parameters for
busulfan in those patients randomized to the busulfan treatment arm. III. Investigate the
prognostic significance for event free survival of prior history of red cell transfusions,
cytogenetic pattern, and of functional drug resistance at diagnosis in these patients. IV.
Estimate the frequencies of cytogenetic and genetic changes during disease progression in
these patients.

OUTLINE: This a randomized, multicenter study. Patients are stratified according to age (40
and under vs 41-55) and diagnosis and International Prognostic Scoring System (IPSS) risk
group (myelodysplastic syndrome (MDS)/IPSS - intermediate 1 vs MDS/IPSS - intermediate 2 vs
MDS/IPSS high risk vs MDS related acute myeloid leukemia). Patients are randomized to one of
two treatment arms. Arm I: Patients receive busulfan IV over 2 hours every 6 hours on days
-7 to -4 for a total of 16 doses. Arm II: Patients receive cyclophosphamide IV over 2 hours
on days -5 and -4. Patients receive total body irradiation (TBI) twice a day on days -3 to
-1; peripheral blood stem cell transplantation from genotypically HLA identical sibling on
day 0; cyclosporine IV every 12 hours on days -1 to 60, and then tapering in the absence of
graft versus host disease; and methotrexate IV on days 1, 3, 6, and 11. Patients are
followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this
study over 5 years.