Phase I/II Study of Intravenous (IV) Busulfan and Etoposide (VP-16) Combined With Escalated Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Advanced Myeloid Malignancies
I. To establish the maximum tolerated dose (MTD) of a large field image-guided IMRT, using
helical tomotherapy, when given in combination with IV busulfan and VP-16 as a preparative
regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical
sibling in patients with advanced myeloid malignancies. (Phase I) II. To describe the
toxicities at each dose level studied. (Phase I) III. To estimate the radiation doses to the
whole body, normal organs, and bone marrow through serial imaging studies following the
administration of IMRT. (Phase I) IV. To estimate the overall survival probability,
disease-free survival probability, and relapse rate associated with this preparative
regimen. (Phase II) V. To characterize the treatment related mortality and toxicity profile
(early/late) associated with this regimen. (Phase II) VI. To descriptively compare the
outcomes of patients treated on this protocol to a comparable patient population conditioned
with whole-body radiotherapy. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy
followed by a phase II study.
PREPARATIVE CHEMOTHERAPY: Patients receive busulfan IV once daily over 2 hours on days -15
and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day
-3. Patients undergo image-guided intensity-modulated radiation therapy using helical
tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or
bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes
After completion of study treatment, patients are followed periodically for 1 year and then
annually for 2 years thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of intensity-modulated radiation therapy (Phase I)
18 months post therapy
Beckman Research Institute
United States: Institutional Review Board
|City of Hope||Duarte, California 91010|