Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

A 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01238211
• Other study ID #: NCI-2011-02615
• Secondary ID: NCI-2011-02615CD
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2010
• Est. completion date: March 15, 2021

Study information

• Verified date: January 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 15, 2021
• Est. primary completion date: July 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• 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; q22.1); RUNX1-RUNX1T1
• Core Binding Factor Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Secondary Acute Myeloid Leukemia
• Therapy-Related Acute Myeloid Leukemia

Intervention

Drug:
• Cytarabine
Given IV
• Dasatinib
Given PO
• Daunorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
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	University of Illinois	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	North Shore University Hospital	Manhasset	New York
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	AdventHealth Orlando	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	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	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Munson Medical Center	Traverse City	Michigan
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30 Day Survival Rate	Percentage of participants who were alive 30 days after starting induction treatment.	30 days
Secondary	Event-free Survival	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).	1 year
Secondary	Complete Response Rate	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).	60 months
Secondary	Cumulative Incidence of Relapse		60 months
Secondary	Cumulative Incidence of Death		36 months
Secondary	Disease-free Survival	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.	3 years
Secondary	Overall Survival	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.	3 years