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A Phase I/II Study of High-Dose Deoxyazacytidine, Busulfan, and Cyclophosphamide With Allogeneic Stem Cell Transplantation for Hematologic Malignancies

Phase 1/Phase 2
15 Years
55 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria

DISEASE CHARACTERISTICS: Acute leukemia past first remission or induction failure Chronic
myelogenous leukemia in accelerated phase or blast crisis

PATIENT CHARACTERISTICS: Age: 15 to 55 Performance status: Zubrod 0-2 Life expectancy:
Life expectancy not severely limited by concurrent illness Hematopoietic: Not specified
Hepatic: No evidence of chronic active hepatitis or cirrhosis Bilirubin no greater than 2
times upper limit of normal SGPT no greater than 4 times upper limit of normal Renal:
Creatinine no greater than 1.5 mg/dL Cardiovascular: Left ventricular ejection fraction at
least 50% No uncontrolled arrhythmias or symptomatic cardiac disease Pulmonary: FEV1, FVC,
and DLCO at least 50% No symptomatic pulmonary disease Other: Related donor who is
HLA-identical required No effusion or ascites greater than 1 L prior to drainage HIV
negative Not pregnant No active CNS disease


Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Time Frame:

Study Duration 3 Years

Safety Issue:


Principal Investigator

Sergio Giralt, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Federal Government

Study ID:




Start Date:

July 1994

Completion Date:

December 2002

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • Leukemia



University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009