Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia
I. Compare the activity of idarubicin and cytarabine with or without bevacizumab in patients
with newly diagnosed acute myeloid leukemia.
II. Compare the proportion of patients who survive and remain in first complete remission
(CR) one year from achieving CR after treatment with these regimens.
I. Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(< 45 vs 45 to 59), cytogenetics (normal vs -5/-7 vs other), flt 3 status (normal vs
mutated), and type of acute myeloid leukemia (AML) (de novo vs secondary [arising after
cytotoxic therapy or after an antecedent hematologic disorder, defined as a documented
abnormality in blood count for >= 3 months before diagnosis of AML]. Patients who require
treatment before cytogenetics or flt 3 status is known (e.g., patients with WBC > 50,000 OR
with organ dysfunction thought to be due to blast infiltration) are stratified only
according to age and type of AML. Induction therapy: Patients are randomized to 1 of 2
Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously
over 24 hours on days 1-4.
Arm II: Patients receive idarubicin and cytarabine as in arm I. Patients also receive
bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission
(CR) after the first induction course may receive a second induction course approximately 28
days* later. Patients who do not achieve CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration
schedule, once every 21 days for 1 year from CR date.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28
days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously
over 24 hours on days 1-4.
Course 3: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24
hours on days 1-2. After completion of the 4 post-CR chemotherapy courses, patients in arm I
induction therapy do not receive further therapy. Patients in arm II induction therapy
continue to receive bevacizumab as described above.After completion of study treatment,
patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 60-120 patients (30-60 per treatment arm) will be accrued for
this study within 12-30 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients who remain alive in the first complete remission (CR) 1 year from achievement of CR assessed every 3 weeks for 1 year
Fisher's exact test will be used to compare the proportion of patients alive in CR 13 months from registration date. The test has approximately 89% power to detect an absolute increase of 20% in this proportion, testing at the one-sided 0.15 significance level.
13 months from registration
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|