Phase I-II Study of Escalating Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy in Combination With Etoposide (VP16) and Cytoxan as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation for Patients With Poor Risk Acute Lymphocytic Leukemia (ALL) or Poor Risk Acute Myelogenous Leukemia (AML)
OBJECTIVES: I. To establish the maximum tolerated dose [MTD] of large field image-guided
IMRT, using helical tomotherapy when given in combination with intravenous cyclophosphamide
and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation
(HSCT) from an human leukocyte antigen (HLA)-identical sibling or unrelated donor in
patients with ALL or AML with induction failure or in relapse. (Phase I) II. To describe the
toxicity at each dose level standard. (Phase I) III. To collect data on the radiation dose
to normal organs and bone marrow using tomotherapy targeted total-body irradiation (TBI).
(Phase I) IV. To estimate the overall survival probability, disease free survival
probability and relapse rate associated with this 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 radiation. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy
(IMRT) followed by a phase II study.
PREPARATIVE REGIMEN: Patients undergo IMRT using helical tomotherapy once or twice daily on
days -10 to -6 or -10 to -7. Patients also receive etoposide intravenously (IV) on day -6 or
-5 and cyclophosphamide IV on day -4 or -3.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell or bone marrow
transplantation on day -1 or day 0. After completion of study treatment, patients are
followed up periodically for up to 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of intensity-modulated radiotherapy (Phase I)
Toxicities will be recorded using two distinct grading systems: the modified Bearman scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 3.0 scale.
30 days post transplant
Anthony S. Stein, MD
City of Hope Medical Center
United States: Institutional Review Board
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