Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
This randomized phase II trial is studying how alvocidib, cytarabine, and mitoxantrone hydrochloride work compared to cytarabine and daunorubicin hydrochloride in treating patients with newly diagnosed acute myeloid leukemia. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, mitoxantrone hydrochloride, and daunorubicin hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving alvocidib, cytarabine, and mitoxantrone hydrochloride is more effective than giving cytarabine and daunorubicin hydrochloride in treating patients with acute myeloid leukemia.
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: daunorubicin hydrochloride
Drug: mitoxantrone hydrochloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Complete response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The final analysis will be by Fisher's exact test.
- Incidence of toxicities, characterized as percentages by treatment and grade [ Time Frame: Up to 14 days after completion of study treatment ] [ Designated as safety issue: Yes ]The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
- Disease-free survival [ Time Frame: Time from randomization until death from any cause or relapse or recurrence, assessed up to 5 years ] [ Designated as safety issue: No ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
- Overall survival [ Time Frame: From time of enrollment until time of death, assessed up to 5 years ] [ Designated as safety issue: No ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
- Progression-free survival [ Time Frame: Time from study entry to the first date that recurrent or progressive disease is objectively documented, or death from any cause occurs, assessed up to 5 years ] [ Designated as safety issue: No ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
- Proportion of patients with minimal residual disease [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Comparisons of the treatments with respect to MRD will be based on the proportion of patients with MRD at each time point (e.g., day 14, recovery from induction but before beginning course 2, etc.).
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride)
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.
Other Names:Drug: mitoxantrone hydrochloride
Other Names:Drug: cytarabine
Active Comparator: Arm II (cytarabine, daunorubicin hydrochloride)
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.
Drug: daunorubicin hydrochloride
Other Names:Drug: cytarabine
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 (AML).
I. To evaluate and compare the toxicities of FLAM vs 7+3. II. To compare the 2-year disease-free survival (DFS) and overall survival (OS) in response to FLAM vs 7+3.
III. To detect and compare the presence of minimal-residual disease (MRD) remaining after FLAM vs 7+3.
IV. 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 7+3.
OUTLINE: This is a multicenter study. Patients are stratified according to risk features: age (< 50 vs >= 50), secondary AML (pre-existing myelodysplatic syndrome [MDS], myeloproliferative diseases [MPD], treatment-related [t]-AML, or severe multi-lineage dysplasia) and/or known adverse cytogenetics, and hyperleukocytosis (white blood cells [WBC] >= 50,000/mm^3). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive alvocidib intravenously (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.
|United States, Arizona|
|Mayo Clinic Scottsdale-Phoenix||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Raoul Tibes 480-301-8335 Tibes.Raoul@mayo.edu|
|Principal Investigator: Raoul Tibes|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Jeffrey E. Lancet 813-745-6841 firstname.lastname@example.org|
|Principal Investigator: Jeffrey E. Lancet|
|United States, Georgia|
|Blood and Marrow Transplant Group of Georgia||Recruiting|
|Atlanta, Georgia, United States, 30342|
|Contact: Lawrence E. Morris 404-255-1938 email@example.com|
|Principal Investigator: Lawrence E. Morris|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Olatoyosi M. Odenike 772-702-3354 firstname.lastname@example.org|
|Principal Investigator: Olatoyosi M. Odenike|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287-8936|
|Contact: B. D. Smith 410-287-2935 email@example.com|
|Principal Investigator: B. D. Smith|
|University of Maryland Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201-1595|
|Contact: Maria R. Baer 410-328-8708 firstname.lastname@example.org|
|Principal Investigator: Maria R. Baer|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Mark R. Litzow 507-284-5362 email@example.com|
|Principal Investigator: Mark R. Litzow|
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Matthew C. Foster 919-843-2447 firstname.lastname@example.org|
|Principal Investigator: Matthew C. Foster|
|United States, South Carolina|
|Medical University of South Carolina||Recruiting|
|Charleston, South Carolina, United States, 29425|
|Contact: Robert K. Stuart 843-792-4271 email@example.com|
|Principal Investigator: Robert K. Stuart|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Stephen A. Strickland 800-811-8480 firstname.lastname@example.org|
|Principal Investigator: Stephen A. Strickland|
|United States, Texas|
|Baylor University Medical Center||Recruiting|
|Dallas, Texas, United States, 75246|
|Contact: Moshe Y. Levy 800-422-9567 email@example.com|
|Principal Investigator: Moshe Y. Levy|
|United States, Virginia|
|Virginia Commonwealth University||Recruiting|
|Richmond, Virginia, United States, 23298|
|Contact: Prithviraj Bose 804-828-9723 firstname.lastname@example.org|
|Principal Investigator: Prithviraj Bose|
|Principal Investigator:||B. Smith||Johns Hopkins University|