PRIMARY OBJECTIVES:
I. Compare the event-free survival (EFS) of daunorubicin, cytarabine plus uproleselan
versus daunorubicin and cytarabine in subjects >= age 60 with previously untreated acute
myeloid leukemia. (Phase II) II. Compare the overall survival (OS) of the daunorubicin,
cytarabine plus uproleselan to daunorubicin and cytarabine in this patient population.
(Phase III)
SECONDARY OBJECTIVES:
I. Determine the rates of complete remission (CR), complete remission with incomplete
count recovery (CRi), complete remission with incomplete hematopoietic recovery (CRh) and
cytogenetic complete remission (CCyR) for each chemotherapy regimen.
II. Determine the overall survival (OS), and remission duration of patients for each
chemotherapy regimen.
III. Describe the frequency and severity of adverse events for patients for each
chemotherapy regimen.
IV. Describe the interaction of pretreatment disease and patient characteristics
including morphology, cytogenetics, molecular genetic features, white blood cell (WBC)
count and hemogram, and performance status on clinical outcomes.
CORRELATIVE SCIENCE OBJECTIVES:
I. Correlate specific karyotype groups (normal or various primary and secondary
chromosomal abnormalities) with clinical and laboratory parameters and with response
rates, response duration, survival and cure in patients treated with various induction
and post-induction regimens.
II. Correlate specific karyotype groups with selected molecular abnormalities and with
measurable residual disease.
III. To determine karyotype changes at end of consolidation and the influence of the type
of change (or no change) in karyotype at the end of consolidation on subsequent clinical
course.
IV. To determine karyotype changes at relapse and the influence of the type of change (or
no change) in karyotype at relapse on subsequent clinical course.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: INDUCTION: Patients receive daunorubicin intravenously (IV) on days 1-3 and
cytarabine via continuous intravenous infusion (CIVI) over 168 hours on days 1-7.
Patients with residual disease indicated by bone marrow examination receive a second
induction including daunorubicin IV on days 1-3 and cytarabine CIVI over 12 hours on days
1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats
every 28 days for up to 3 cycles in the absence of disease progression or unacceptable
toxicity.
ARM 2: INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on
days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over
168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone
marrow examination receive a second induction including uprleselan IV QD on day 1 and
then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over
120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and
every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats
every 28 days for up to 3 cycles in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up every 2 months for 1 year,
every 3 months in year 2, and then every 6 months for up to 5 years.
