- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01238211
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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)
Study Overview
Status
Conditions
- Acute Myeloid Leukemia
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
- Secondary Acute Myeloid Leukemia
- Therapy-Related Acute Myeloid Leukemia
- 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
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Delaware
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Lewes, Delaware, United States, 19958
- Beebe Medical Center
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Newark, Delaware, United States, 19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Orlando, Florida, United States, 32803
- AdventHealth Orlando
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Illinois
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Bloomington, Illinois, United States, 61704
- Illinois CancerCare-Bloomington
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Bloomington, Illinois, United States, 61701
- Saint Joseph Medical Center
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Canton, Illinois, United States, 61520
- Illinois CancerCare-Canton
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Canton, Illinois, United States, 61520
- Graham Hospital Association
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Carthage, Illinois, United States, 62321
- Memorial Hospital
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Chicago, Illinois, United States, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States, 60612
- University of Illinois
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Decatur, Illinois, United States, 62526
- Heartland Cancer Research NCORP
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Eureka, Illinois, United States, 61530
- Illinois CancerCare-Eureka
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Eureka, Illinois, United States, 61530
- Eureka Hospital
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Galesburg, Illinois, United States, 61401
- Illinois CancerCare-Galesburg
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Havana, Illinois, United States, 62644
- Mason District Hospital
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Macomb, Illinois, United States, 61455
- Illinois CancerCare-Macomb
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Macomb, Illinois, United States, 61455
- Mcdonough District Hospital
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Normal, Illinois, United States, 61761
- Carle Cancer Institute Normal
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Normal, Illinois, United States, 61761
- Bromenn Regional Medical Center
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Normal, Illinois, United States, 61761
- Illinois CancerCare-Community Cancer Center
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Ottawa, Illinois, United States, 61350
- Illinois CancerCare-Ottawa Clinic
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Ottawa, Illinois, United States, 61350
- Ottawa Regional Hospital and Healthcare Center
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Pekin, Illinois, United States, 61554
- Illinois CancerCare-Pekin
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Pekin, Illinois, United States, 61554
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
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Peoria, Illinois, United States, 61636
- Methodist Medical Center of Illinois
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Peoria, Illinois, United States, 61637
- OSF Saint Francis Medical Center
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Peoria, Illinois, United States, 61615
- Illinois CancerCare-Peoria
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Peoria, Illinois, United States, 61614
- Proctor Hospital
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Peru, Illinois, United States, 61354
- Illinois CancerCare-Peru
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Peru, Illinois, United States, 61354
- Illinois Valley Hospital
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Princeton, Illinois, United States, 61356
- Perry Memorial Hospital
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Spring Valley, Illinois, United States, 61362
- Illinois CancerCare-Spring Valley
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Indiana
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Fort Wayne, Indiana, United States, 46845
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Augusta, Maine, United States, 04330
- Harold Alfond Center for Cancer Care
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Bangor, Maine, United States, 04401
- Eastern Maine Medical Center
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Maryland
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Baltimore, Maryland, United States, 21201
- University of Maryland/Greenebaum Cancer Center
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Elkton, Maryland, United States, 21921
- Christiana Care - Union Hospital
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Battle Creek, Michigan, United States, 49017
- Bronson Battle Creek
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Big Rapids, Michigan, United States, 49307
- Spectrum Health Big Rapids Hospital
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Grand Rapids, Michigan, United States, 49503
- Spectrum Health at Butterworth Campus
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Grand Rapids, Michigan, United States, 49503
- Mercy Health Saint Mary's
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Grand Rapids, Michigan, United States, 49503
- Cancer Research Consortium of West Michigan NCORP
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Muskegon, Michigan, United States, 49444
- Mercy Health Mercy Campus
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Reed City, Michigan, United States, 49677
- Spectrum Health Reed City Hospital
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Traverse City, Michigan, United States, 49684
- Munson Medical Center
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Missouri
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Columbia, Missouri, United States, 65212
- University of Missouri - Ellis Fischel
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center
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New Jersey
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Camden, New Jersey, United States, 08103
- Cooper Hospital University Medical Center
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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Lake Success, New York, United States, 11042
- Northwell Health NCORP
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Lake Success, New York, United States, 11042
- Northwell Health/Center for Advanced Medicine
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Manhasset, New York, United States, 11030
- North Shore University Hospital
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New Hyde Park, New York, United States, 11040
- Long Island Jewish Medical Center
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New York, New York, United States, 10065
- NYP/Weill Cornell Medical Center
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Syracuse, New York, United States, 13210
- State University of New York Upstate Medical University
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North Carolina
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Goldsboro, North Carolina, United States, 27534
- Wayne Memorial Hospital
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
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Vermont
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Berlin, Vermont, United States, 05602
- Central Vermont Medical Center/National Life Cancer Treatment
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Burlington, Vermont, United States, 05405
- University of Vermont and State Agricultural College
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
30 Day Survival Rate
Time Frame: 30 days
|
Percentage of participants who were alive 30 days after starting induction treatment.
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30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free Survival
Time Frame: 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). |
1 year
|
Complete Response Rate
Time Frame: 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).
|
60 months
|
Cumulative Incidence of Relapse
Time Frame: 60 months
|
60 months
|
|
Cumulative Incidence of Death
Time Frame: 36 months
|
36 months
|
|
Disease-free Survival
Time Frame: 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.
|
3 years
|
Overall Survival
Time Frame: 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.
|
3 years
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Cytarabine
- Daunorubicin
- Dasatinib
Other Study ID Numbers
- NCI-2011-02615 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180821 (U.S. NIH Grant/Contract)
- U10CA031946 (U.S. NIH Grant/Contract)
- CDR0000688434
- CALGB-10801 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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