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

NCT ID: NCT01238211

Last Updated: 2023-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-14
• Study Completion Date: 2021-03-15

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.

Conditions

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; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (daunorubicin hydrochloride, cytarabine, 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.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Given IV

Dasatinib

Intervention Type: DRUG

Given PO

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Cytarabine

Given IV

Intervention Type: DRUG

Dasatinib

Given PO

Intervention Type: DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

.beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; BMS-354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guido Marcucci

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

AdventHealth Orlando

Orlando, Florida, United States

Saint Joseph Medical Center

Bloomington, Illinois, United States

Illinois CancerCare-Bloomington

Bloomington, 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 Illinois

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Heartland Cancer Research NCORP

Decatur, Illinois, United States

Eureka Hospital

Eureka, Illinois, United States

Illinois CancerCare-Eureka

Eureka, Illinois, 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

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

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

Proctor Hospital

Peoria, 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

Illinois CancerCare-Peru

Peru, Illinois, United States

Illinois Valley Hospital

Peru, Illinois, United States

Perry Memorial Hospital

Princeton, Illinois, United States

Illinois CancerCare-Spring Valley

Spring Valley, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Eastern Maine Medical Center

Bangor, Maine, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Christiana Care - Union Hospital

Elkton, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, 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

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Spectrum Health Reed City Hospital

Reed City, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Northwell Health NCORP

Lake Success, New York, United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States

North Shore University Hospital

Manhasset, New York, 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

State University of New York Upstate Medical University

Syracuse, New York, United States

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Countries

United States

References

Marcucci G, Geyer S, Laumann K, Zhao W, Bucci D, Uy GL, Blum W, Eisfeld AK, Pardee TS, Wang ES, Stock W, Kolitz JE, Kohlschmidt J, Mrozek K, Bloomfield CD, Stone RM, Larson RA. Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801. Blood Adv. 2020 Feb 25;4(4):696-705. doi: 10.1182/bloodadvances.2019000492.

Reference Type: DERIVED

PMID: 32092139 (View on PubMed)

Yin J, LaPlant B, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar SJ. Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614). Blood Adv. 2019 Jun 11;3(11):1714-1721. doi: 10.1182/bloodadvances.2018026112.

Reference Type: DERIVED

PMID: 31171508 (View on PubMed)

Other Identifiers

NCI-2011-02615

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000688434

Identifier Type: -

Identifier Source: secondary_id

CALGB-10801

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-10801

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02615

Identifier Type: -

Identifier Source: org_study_id