Trial Information

Gemtuzumab Ozogamicin (GO), Fludarabine, And Low-Dose TBI Followed By Donor Stem Cell Transplantation For Patients With Advanced Acute Myeloid Leukemia Or Myelodysplastic Syndrome

OBJECTIVES: I. Determine the response and disease-free survival at 1 year of patients with
advanced acute myeloid leukemia or myelodysplastic syndrome treated with gemtuzumab
ozogamicin, fludarabine, and total body irradiation followed by allogeneic peripheral blood
stem cell or bone marrow transplantation with cyclosporine and mycophenolate mofetil. II.
Determine the leukemic blast clearance from the blood and marrow in these patients treated
with this regimen. III. Determine the safety and pharmacokinetics of gemtuzumab ozogamicin
as part of this regimen in these patients. IV. Determine the incidence of donor stem cell
engraftment in these patients. V. Determine the incidence and severity of graft-versus-host
disease in these patients treated with this regimen. VI. Determine whether donor lymphocyte
infusion can be safely used in the patients with mixed or full donor chimerism to eliminate
persistent or progressive disease.

OUTLINE: Patients receive gemtuzumab ozogamicin IV over 2 hours on days -21 (first 5
patients) or -14 (subsequent patients) and -7, and fludarabine IV over 2 hours on days -4 to
-2. Patients undergo total body irradiation followed by infusion of allogeneic peripheral
blood stem cells or bone marrow on day 0. Patients receive oral or IV cyclosporine 2-3 times
daily on days -3 to 56 (if related donor) or 100 (if unrelated donor) and oral or IV
mycophenolate mofetil twice daily on days 0 to 27 (if related donor) or 40 (if unrelated
donor). Patients receive 2 doses of intrathecal methotrexate prior to transplant and an
additional 4 doses after transplant. Patients with cerebral spinal fluid (CSF) positive for
malignant cells instead receive intrathecal cytarabine, methotrexate and hydrocortisone
prior to transplant twice weekly until CSF blasts clear. Patients with persistent or
recurrent disease after transplant may receive up to 3 donor lymphocyte infusions if
graft-versus-host disease is less than grade II and they have greater than 5% donor CD3
cells. Patients are followed at 6 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 1-2
years.