Randomized Phase II Trial of Timed Sequential Therapy (TST) With Alvocidib (Flavopiridol), Ara-C and Mitoxantrone (FLAM) vs. "7+3" for Adults Age 70 and Under With Newly Diagnosed Acute Myelogenous Leukemia (AML)
I. To compare the rate of complete remission (CR) after 1 course of induction therapy with
the timed-sequential combination of alvocidib (flavopiridol), cytarabine (cytosine
arabinoside [ara-C]), and mitoxantrone hydrochloride (FLAM) vs traditional "7+3" cytarabine
and daunorubicin hydrochloride (ara-C + Daunorubicin) for adults (age 18 to 70) with newly
diagnosed, previously untreated, intermediate-risk or poor-risk acute myelogenous leukemia
I. To evaluate and compare the toxicities of FLAM vs 7+3.To compare the 2-year disease-free
survival (DFS) and overall survival (OS) in response to FLAM vs 7+3.
II. To detect and compare the presence of minimal-residual disease (MRD) remaining after
FLAM vs 7+3.
III. To determine the expression of ABC transport proteins multidrug resistance 1 (MDR1,
ABCB1) and breast cancer resistance protein (BCRP, ABCG2) on AML blasts pretreatment and
correlate the expressions of one or both proteins with CR and DFS in response to FLAM vs
OUTLINE: This is a multicenter study. Patients are stratified according to risk features:
age (< 50 vs ≥ 50), secondary AML (pre-existing MDS, MPD, t-AML, or severe multi-lineage
dysplasia) and/or known adverse cytogenetics, and hyperleukocytosis (WBC ≥ 50,000/mm³).
Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV over 72 hours on
days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Patients who achieve
complete or partial response to the first course (completion of all doses) may receive a
second course of treatment or high-dose cytarabine after 21-63 days following blood count
recovery, and/or undergo allogeneic bone marrow transplant.
ARM II: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin
hydrochloride IV on days 1-3. Patients who have residual disease on day 14 may receive
additional cytarabine for 5 days and daunorubicin hydrochloride for 2 days. Patients may
undergo blood and bone marrow collection for correlative studies.
After completion of study therapy, patients are followed up every 3 months for 2 years,
every 6 months for 5 years, and then annually thereafter.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete response rate
The final analysis will be by Fisher's exact test.
Up to 5 years
Johns Hopkins University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|Mayo Clinic||Rochester, Minnesota 55905|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Medical University of South Carolina||Charleston, South Carolina 29425-0721|
|Rush University Medical Center||Chicago, Illinois 60612-3824|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Northwestern University||Chicago, Illinois 60611|
|Blood and Marrow Transplant Group of Georgia||Atlanta, Georgia 30342-1601|
|Virginia Commonwealth University||Richmond, Virginia|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Scottsdale Healthcare||Scottsdale, Arizona 85251|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|