Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
|ClinicalTrials.gov Identifier: NCT01349972|
Recruitment Status : Completed
First Posted : May 9, 2011
Results First Posted : June 6, 2017
Last Update Posted : July 31, 2017
|Condition or disease||Intervention/treatment||Phase|
|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: alvocidib Drug: daunorubicin hydrochloride Drug: mitoxantrone hydrochloride Drug: cytarabine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||172 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||April 2011|
|Actual Primary Completion Date :||May 2014|
|Actual Study Completion Date :||May 2014|
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
- Complete Response Rate [ Time Frame: 3 years ]Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/cu mm and a platelet count of 100,000/cu mm, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. These criteria are taken from Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-474
- Incidence of Toxicities, Characterized by Number of Events by Treatment and Grade [ Time Frame: Up to 14 days after completion of study treatment ]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 2 years ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated. Disease-free survival Overall survival was defined from date of randomization to death or last known follow-up. Event free survival was defined as date of randomization to the first occurrence of persistent AML after 1 cycle of induction, relapse or death. Patients were censored for event free survival if they had received non-protocol therapy or a stem cell transplant.
- Overall Survival [ Time Frame: 4 years ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
- Number of Patients With Minimal Residual Disease [ Time Frame: From study start to 14 days after the start of treatment ]Comparisons of the treatments with respect to MRD will be based on the number of patients with MRD at day 14 after the start of treatment.
- Progression-free Survival [ Time Frame: 4 years ]Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01349972
|United States, Arizona|
|Mayo Clinic Scottsdale-Phoenix|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Blood and Marrow Transplant Group of Georgia|
|Atlanta, Georgia, United States, 30342|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|Baylor University Medical Center|
|Dallas, Texas, United States, 75246|
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||B. Smith||Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center|