Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
- Conditions
- Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11Therapy-Related Acute Myeloid LeukemiaAcute Myeloid LeukemiaAcute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeAdult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1Core Binding Factor Acute Myeloid LeukemiaSecondary Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT01238211
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial studies the side effects and how well giving combination chemotherapy together with dasatinib works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with dasatinib may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of dasatinib 100 mg/day given after intensive induction (daunorubicin hydrochloride \[daunorubicin\]/cytarabine), and consolidation chemotherapy (high-dose cytarabine) and as single agent in maintenance therapy to newly diagnosed patients with core binding factor acute myeloid leukemia (AML).
II. 30-day survival rate during induction (the lack of early/hypoplastic death).
III. The absence of pleural or pericardial effusion, and absence of liver toxicity that exceeds grade 2.
SECONDARY OBJECTIVES:
I. To assess clinical outcomes such as event-free survival (EFS), complete response (CR) rate, cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS).
II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.
III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.
OUTLINE:
INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily (QD) on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20 % and leukemia blasts \>= 5%) receive a second course of induction therapy.
INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy.
CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then every year for up to 10 years from study entry.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
-
Documentation of disease as assessed by the Alliance reference laboratory at the Ohio State University per Cancer and Leukemia Group B (CALGB) 20202, molecular diagnosis of core-binding factor (CBF) acute myeloid leukemia (AML) by reverse transcriptase polymerase chain reaction (RT-PCR) positive for RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22) (or a variant form) or CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (any % bone marrow or blood blasts render the diagnosis of CBF AML based on the World Health Organization [WHO] classification)
-
No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea,
- Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose only),
- Growth factor/cytokine support/non-cytotoxic molecular-targeted agents
-
AML patients with a history of antecedent myelodysplasia (MDS) remain eligible for treatment on this trial
-
Patients who have developed therapy related myeloid neoplasm (t-MN) after prior radiation therapy or chemotherapy for another cancer or disorder are eligible
-
Left ventricular ejection fraction >= lower limit of institutional normal by multigated acquisition (MUGA) or echocardiogram (ECHO) scan
-
Patients must not have had myocardial infarction within 6 months of registration
-
Patients must not have had ventricular tachyarrhythmia within 6 months of registration
-
Patients must have no major conduction abnormality (unless a cardiac pacemaker is present)
-
Bilirubin must not be < 2.5 times upper limit of normal
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Patients must be non-pregnant and non-nursing; pregnant or nursing patients may not be enrolled; women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration; women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, before she begins dasatinib therapy, during treatment and at least 12 weeks after treatment is complete; "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months
-
Patients with congenital long QT syndrome or non-congenital corrected QT (QTc) prolongation (defined as a QTc interval consistently equal to or greater than 480 msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of other medications prior to start of treatment are excluded
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (daunorubicin hydrochloride, cytarabine, dasatinib) Daunorubicin Hydrochloride INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy. INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy. Treatment (daunorubicin hydrochloride, cytarabine, dasatinib) Laboratory Biomarker Analysis INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy. INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy. Treatment (daunorubicin hydrochloride, cytarabine, dasatinib) Dasatinib INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy. INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy. Treatment (daunorubicin hydrochloride, cytarabine, dasatinib) Cytarabine INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy. INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
- Primary Outcome Measures
Name Time Method 30 Day Survival Rate 30 days Percentage of participants who were alive 30 days after starting induction treatment.
- Secondary Outcome Measures
Name Time Method Cumulative Incidence of Relapse 60 months Complete Response Rate 60 months Percentage of participants who achieve a CR. Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).
Cumulative Incidence of Death 36 months Event-free Survival 1 year Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The 1 year EFS rate with 95% CI was estimated using the Kaplan-Meier method,
Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).Disease-free Survival 3 years Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The 3 year DFS rate with 95% CI was estimated using the Kaplan-Meier method.
Overall Survival 3 years Overall survival (OS) is defined as time from registration to death. The 3 year OS rate with 95% CI was estimated using the Kaplan-Meier method.
Trial Locations
- Locations (65)
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Heartland Cancer Research NCORP
🇺🇸Decatur, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Community Cancer Center
🇺🇸Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
🇺🇸Fort Wayne, Indiana, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Christiana Care - Union Hospital
🇺🇸Elkton, Maryland, United States
Spectrum Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Spectrum Health Big Rapids Hospital
🇺🇸Big Rapids, Michigan, United States
Mercy Health Mercy Campus
🇺🇸Muskegon, Michigan, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Carle Cancer Institute Normal
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Mercy Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
Northwell Health NCORP
🇺🇸Lake Success, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸Berlin, Vermont, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Cancer Research Consortium of West Michigan NCORP
🇺🇸Grand Rapids, Michigan, United States
Illinois CancerCare-Spring Valley
🇺🇸Spring Valley, Illinois, United States