HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC SYNDROME - A PHASE 2 STUDY
- To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic cell
transplantation with a reduced-intensity conditioning regimen of busulfan, fludarabine
phosphate, and anti-thymocyte globulin in patients with hematologic malignancies or
OUTLINE: Before receiving the reduced-intensity conditioning regimen, patients receive one
dose of intrathecal (IT) methotrexate, then leucovorin calcium IV or orally 4 hours after
methotrexate and every 6 hours for a total of 8 doses.
- Reduced-intensity conditioning regimen: Patients receive busulfan IV over 6 hours on
days -7 and -6, fludarabine phosphate IV over 30 minutes on days -7 to -2,
anti-thymocyte globulin (ATG) IV over 4 hours on days -4 to -1, and methylprednisolone
IV over 30 minutes on days -4 to -1.
- HLA-haploidentical familial donor hematopoietic stem cell transplantation (HSCT):
Patients undergo allogeneic HSCT over 1 hour on days 0 and 1.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV* over
2-4 hours every 12 hours on days -1 to 30 followed by a taper until day 60 and
methotrexate IV on days 2, 4 , 7, and 12.
NOTE: *Cyclosporine can be given orally once oral medication can be tolerated
- CNS prophylaxis: When blood counts recover, patients with acute leukemia or chronic
myelogenous leukemia in blastic crisis resume IT methotrexate once every 2 weeks for a
total of 4 doses (including the dose given before the conditioning regimen) and
leucovorin calcium IV or orally 4 hours after (each dose of methotrexate) and every 6
hours for a total of 8 doses.
After completion of study treatment, patients are followed periodically for up to 3 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
leukemia CR, CR duration
about 4-8 weeks after transplantation
Kyoo H. Lee, MD
Asan Medical Center
Korea: Food and Drug Administration