Overview

This trial is active, not recruiting.

Conditions acute myeloid leukemia arising from previous myelodysplastic syndrome, adult acute myeloid leukemia with inv(16)(p13.1q22); cbfb-myh11, adult acute myeloid leukemia with t(16;16)(p13.1;q22); cbfb-myh11, adult acute myeloid leukemia with t(8;21)(q22;q22); runx1-runx1t1, secondary acute myeloid leukemia, untreated adult acute myeloid leukemia
Treatments daunorubicin hydrochloride, cytarabine, dasatinib, laboratory biomarker analysis
Phase phase 2
Target BCR-ABL
Sponsor National Cancer Institute (NCI)
Start date December 2010
End date July 2013
Trial size 61 participants
Trial identifier NCT01238211, CALGB 10801, CALGB-10801, CDR0000688434, NCI-2011-02615, U10CA031946, U10CA180821

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 or by stopping them from dividing. 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
daunorubicin hydrochloride DNM
Given IV
cytarabine CHX-3311
Given IV
dasatinib BMS-354825
Given PO
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
30 Day Survival Rate
time frame: 30 days

Secondary Outcomes

Measure
Event-free Survival
time frame: Up to 10 years
Complete Response Rate
time frame: Up to 10 years
Cumulative Incidence of Relapse
time frame: Up to 10 years
Cumulative Incidence of Death
time frame: Up to 10 years
Disease-free Survival
time frame: Up to 10 years
Overall Survival
time frame: Up to 10 years

Eligibility Criteria

Male or female participants at least 18 years old.

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 runt-related transcription factor 1(RUNX1)-runt-related transcription factor 1; translocated to 1 (RUNX1T1) fusion transcript resulting from t(8;21)(q22;q22) (or a variant form) or core binding factor β-chain (CBFB)-myosin heavy chain 11 gene (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 and/or cytokine support and/or 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

Additional Information

Official title Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)
Principal investigator Guido Marcucci
Description PRIMARY OBJECTIVES: I. To assess the safety and tolerability of dasatinib with intensive induction therapy (daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed core-binding factor acute myeloid leukemia (AML). 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) of patients treated with these regimens. 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. Treatment repeats every 28 days for 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).