Acute Myeloid Leukemia Clinical Trial
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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.
Full 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.
Eligibility Criteria
Inclusion Criteria:
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
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
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There are 54 Locations for this study
Lewes Delaware, 19958, United States
Newark Delaware, 19718, United States
Orlando Florida, 32803, United States
Bloomington Illinois, 61701, United States
Bloomington Illinois, 61704, United States
Canton Illinois, 61520, United States
Canton Illinois, 61520, United States
Carthage Illinois, 62321, United States
Chicago Illinois, 60612, United States
Chicago Illinois, 60637, United States
Decatur Illinois, 62526, United States
Eureka Illinois, 61530, United States
Eureka Illinois, 61530, United States
Galesburg Illinois, 61401, United States
Havana Illinois, 62644, United States
Macomb Illinois, 61455, United States
Macomb Illinois, 61455, United States
Normal Illinois, 61761, United States
Normal Illinois, 61761, United States
Normal Illinois, 61761, United States
Ottawa Illinois, 61350, United States
Ottawa Illinois, 61350, United States
Pekin Illinois, 61554, United States
Pekin Illinois, 61554, United States
Peoria Illinois, 61614, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61636, United States
Peoria Illinois, 61637, United States
Peru Illinois, 61354, United States
Peru Illinois, 61354, United States
Princeton Illinois, 61356, United States
Spring Valley Illinois, 61362, United States
Fort Wayne Indiana, 46845, United States
Iowa City Iowa, 52242, United States
Augusta Maine, 04330, United States
Bangor Maine, 04401, United States
Baltimore Maryland, 21201, United States
Elkton Maryland, 21921, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02115, United States
Boston Massachusetts, 02215, United States
Battle Creek Michigan, 49017, United States
Big Rapids Michigan, 49307, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Muskegon Michigan, 49444, United States
Reed City Michigan, 49677, United States
Traverse City Michigan, 49684, United States
Columbia Missouri, 65212, United States
Saint Louis Missouri, 63110, United States
Lebanon New Hampshire, 03756, United States
Camden New Jersey, 08103, United States
Buffalo New York, 14263, United States
Lake Success New York, 11042, United States
Lake Success New York, 11042, United States
Manhasset New York, 11030, United States
New Hyde Park New York, 11040, United States
New York New York, 10065, United States
Syracuse New York, 13210, United States
Goldsboro North Carolina, 27534, United States
Winston-Salem North Carolina, 27157, United States
Columbus Ohio, 43210, United States
Berlin Vermont, 05602, United States
Burlington Vermont, 05405, United States
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