A Phase I/II Study of High-Dose Deoxyazacytidine, Busulfan, and Cyclophosphamide With Allogeneic Stem Cell Transplantation for Hematologic Malignancies
OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in combination with
busulfan and cyclophosphamide in patients with hematologic malignancies. II. Establish the
pharmacokinetics of decitabine and busulfan in this patient population. III. Determine the
effectiveness of this combination in achieving durable complete remission in patients with
chronic myelogenous leukemia (CML) in blast crisis or acute myelogenous leukemia (AML) in
relapse undergoing allogeneic stem cell transplantation.
OUTLINE: In cohorts of 3, patients receive escalating doses of decitabine (DAC) IV over 4
hours on days -8 and -7. Busulfan is administered orally every 6 hours on consecutive days
-6 through -4. Cyclophosphamide is given by vein (IV) over 1 hour on consecutive days -3 and
-2. The maximum tolerated dose of DAC is defined as the dose at which 2 patients experience
dose limiting toxicity. Donors receive filgrastim subcutaneously (SQ) daily every 12 hours
starting 2-4 days prior to the first stem cell collection and before DAC infusion.
Leukapheresis is conducted daily. If insufficient number of cells are collected, blood
marrow is harvested for supplementation. Stem cells are infused on day 0. For graft vs host
disease prophylaxis (GVHD), patients receive tacrolimus IV beginning one day before stem
cell infusion, then orally following tolerance to tacrolimus. Patients intolerant to
tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and
engraftment. All patients receive methylprednisolone given according to clinical grade of
GVHD procedures. For CNS prophylaxis, methotrexate is given intrathecally or
intraventricularly monthly, beginning on the second month through the eighth month of
treatment. Allogeneic patients are followed until the end of 1 year.
PROJECTED ACCRUAL: An estimated 30 allogeneic recipients will be recruited in 2 years for
the expected study duration of 2-3 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose
Study Duration 3 Years
Sergio Giralt, MD
M.D. Anderson Cancer Center
United States: Federal Government
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|