Gemtuzumab Ozogamicin, Fludarabine, and Total-body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome
RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells.
PURPOSE: Phase II trial to study the effectiveness of gemtuzumab ozogamicin combined with fludarabine and total-body irradiation followed by donor peripheral stem cell or bone marrow transplantation in treating patients who have advanced acute myeloid leukemia or myelodysplastic syndrome.
|Leukemia Myelodysplastic Syndromes||Drug: cyclosporine Drug: fludarabine phosphate Drug: gemtuzumab ozogamicin Drug: methotrexate Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 2|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Gemtuzumab Ozogamicin (GO), Fludarabine, And Low-Dose TBI Followed By Donor Stem Cell Transplantation For Patients With Advanced Acute Myeloid Leukemia Or Myelodysplastic Syndrome|
|Study Start Date:||October 2000|
|Study Completion Date:||July 2002|
|Primary Completion Date:||July 2002 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00008151
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Eric Sievers, MD||Fred Hutchinson Cancer Research Center|