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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01238211
• Collaborator: (none)
• Enrollment: 61
• Locations: 65
• Arm: 1
• Patients Per Site: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Cytarabine; Drug: Dasatinib; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

2. 30-day survival rate during induction (the lack of early/hypoplastic death).

3. The absence of pleural or pericardial effusion, and absence of liver toxicity that exceeds grade 2.

SECONDARY OBJECTIVES:

1. 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).

2. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.

3. 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 Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Dec 14, 2010
• Actual Primary Completion Date: Jul 17, 2015

Arms and Interventions

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.

Drug: Cytarabine; Given IV; Other 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 ; Drug: Dasatinib; Given PO; Other Names: BMS-354825 Dasatinib Hydrate Dasatinib Monohydrate Sprycel ; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. 30 Day Survival Rate [30 days]

   Percentage of participants who were alive 30 days after starting induction treatment.

Secondary Outcome Measures

1. Event-free Survival [Up to 10 years]

   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 median EFS 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).

2. Complete Response Rate [Up to 10 years]

   Percentage of participants who achieve a CR. CR is defined in the above outcome measure.

3. Cumulative Incidence of Relapse [Up to 10 years]

4. Cumulative Incidence of Death [Up to 10 years]

5. Disease-free Survival [Up to 10 years]

   Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The median DFS with 95% CI was estimated using the Kaplan-Meier method.

6. Overall Survival [Up to 10 years]

   Overall survival (OS) is defined as time from registration to death. The median OS with 95% CI was estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beebe Medical Center	Lewes	Delaware	United States	19958
2	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
3	AdventHealth Orlando	Orlando	Florida	United States	32803
4	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
5	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
6	Graham Hospital Association	Canton	Illinois	United States	61520
7	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
8	Memorial Hospital	Carthage	Illinois	United States	62321
9	University of Illinois	Chicago	Illinois	United States	60612
10	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
11	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
12	Eureka Hospital	Eureka	Illinois	United States	61530
13	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
14	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
15	Mason District Hospital	Havana	Illinois	United States	62644
16	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
17	Mcdonough District Hospital	Macomb	Illinois	United States	61455
18	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
19	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
20	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
21	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
22	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
23	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
24	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
25	Proctor Hospital	Peoria	Illinois	United States	61614
26	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
27	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
28	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
29	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
30	Illinois Valley Hospital	Peru	Illinois	United States	61354
31	Perry Memorial Hospital	Princeton	Illinois	United States	61356
32	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
33	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
34	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
35	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
36	Eastern Maine Medical Center	Bangor	Maine	United States	04401
37	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
38	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
39	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
40	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
41	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
42	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
43	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
44	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
45	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
46	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
47	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
48	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
49	Munson Medical Center	Traverse City	Michigan	United States	49684
50	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
51	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
52	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
53	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
54	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
55	Northwell Health NCORP	Lake Success	New York	United States	11042
56	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
57	North Shore University Hospital	Manhasset	New York	United States	11030
58	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
59	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
60	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
61	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
62	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
63	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
64	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
65	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Guido Marcucci, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01238211
• Other Study ID Numbers: NCI-2011-02615; NCI-2011-02615; CDR0000688434; CALGB-10801; CALGB-10801; U10CA180821; U10CA031946
• First Posted: Nov 10, 2010
• Last Update Posted: Jul 19, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Cytarabine; Daunorubicin; Dasatinib

Study Results

Participant Flow

Recruitment Details	Between April 2011 and January 2013, 61 participants were recruited.

Arm/Group Title	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
Arm/Group Description	INDUCTION THERAPY: daunorubicin hydrochloride IV (60 mg/m^2)on days 1-3, cytarabine IV (200 mg/m^2) continuously over 168 hours on days 1-7, and dasatinib PO (100 mg) once daily on days 8-21. Patients achieving a response go to consolidation therapy, and patients not achieving a receive a second course of induction therapy. CONSOLIDATION THERAPY: high-dose cytarabine IV (patients < Age 60: 3000 mg/m^2, Age >= 1000 mg/m^2)over 3 hours on days 1, 3, and 5, and dasatinib PO (100 mg) once daily 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: dasatinib PO (100 mg) once daily for 12 months or relapse.
Period Title: Overall Study
STARTED	61
COMPLETED	3
NOT COMPLETED	58

Baseline Characteristics

Arm/Group Title	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
Arm/Group Description	INDUCTION THERAPY: daunorubicin hydrochloride IV (60 mg/m^2)on days 1-3, cytarabine IV (200 mg/m^2) continuously over 168 hours on days 1-7, and dasatinib PO (100 mg) once daily on days 8-21. Patients achieving a response go to consolidation therapy, and patients not achieving a receive a second course of induction therapy. CONSOLIDATION THERAPY: high-dose cytarabine IV (patients < Age 60: 3000 mg/m^2, Age >= 1000 mg/m^2)over 3 hours on days 1, 3, and 5, and dasatinib PO (100 mg) once daily 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: dasatinib PO (100 mg) once daily for 12 months or relapse.
Overall Participants	61
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	30 49.2%
Male	31 50.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	54 88.5%
Unknown or Not Reported	7 11.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.6%
Native Hawaiian or Other Pacific Islander	1 1.6%
Black or African American	5 8.2%
White	46 75.4%
More than one race	0 0%
Unknown or Not Reported	8 13.1%
Region of Enrollment (participants) [Number]
United States	61 100%

Outcome Measures

1. Primary Outcome

Title	30 Day Survival Rate
Description	Percentage of participants who were alive 30 days after starting induction treatment.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
Arm/Group Description	INDUCTION THERAPY: daunorubicin hydrochloride IV (60 mg/m^2)on days 1-3, cytarabine IV (200 mg/m^2) continuously over 168 hours on days 1-7, and dasatinib PO (100 mg) once daily on days 8-21. Patients achieving a response go to consolidation therapy, and patients not achieving a receive a second course of induction therapy. CONSOLIDATION THERAPY: high-dose cytarabine IV (patients < Age 60: 3000 mg/m^2, Age >= 1000 mg/m^2)over 3 hours on days 1, 3, and 5, and dasatinib PO (100 mg) once daily 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: dasatinib PO (100 mg) once daily for 12 months or relapse.
Measure Participants	61
Number (95% Confidence Interval) [percentage of participants]	97 159%

2. Secondary Outcome

Title	Event-free Survival
Description	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 median EFS 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).
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Complete Response Rate
Description	Percentage of participants who achieve a CR. CR is defined in the above outcome measure.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Cumulative Incidence of Relapse
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Cumulative Incidence of Death
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Disease-free Survival
Description	Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The median DFS with 95% CI was estimated using the Kaplan-Meier method.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) is defined as time from registration to death. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Only 55 participants were evaluable for adverse events at the time of analysis.
Arm/Group Title	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
Arm/Group Description	CONTINUATION THERAPY: dasatinib PO (100 mg) once daily for 12 months or relapse.
All Cause Mortality
	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
	Affected / at Risk (%)	# Events
Total	27/55 (49.1%)
Blood and lymphatic system disorders
Anemia	26/55 (47.3%)	41
Blood and lymphatic system disorders - Other	1/55 (1.8%)	1
Disseminated intravascular coagulation	1/55 (1.8%)	1
Febrile neutropenia	18/55 (32.7%)	25
Cardiac disorders
Atrial fibrillation	2/55 (3.6%)	2
Atrial flutter	1/55 (1.8%)	1
Cardiac arrest	1/55 (1.8%)	1
Chest pain - cardiac	2/55 (3.6%)	2
Palpitations	1/55 (1.8%)	1
Sinus tachycardia	11/55 (20%)	13
Supraventricular tachycardia	1/55 (1.8%)	1
Ventricular arrhythmia	1/55 (1.8%)	1
Ventricular tachycardia	2/55 (3.6%)	2
Endocrine disorders
Hyperthyroidism	1/55 (1.8%)	1
Eye disorders
Blurred vision	1/55 (1.8%)	1
Conjunctivitis	1/55 (1.8%)	1
Dry eye	1/55 (1.8%)	1
Eye disorders - Other	1/55 (1.8%)	1
Gastrointestinal disorders
Abdominal distension	1/55 (1.8%)	1
Abdominal pain	4/55 (7.3%)	4
Ascites	1/55 (1.8%)	1
Colitis	1/55 (1.8%)	1
Constipation	6/55 (10.9%)	7
Dental caries	1/55 (1.8%)	1
Diarrhea	13/55 (23.6%)	17
Dyspepsia	2/55 (3.6%)	2
Dysphagia	1/55 (1.8%)	1
Fecal incontinence	1/55 (1.8%)	1
Flatulence	1/55 (1.8%)	1
Gastritis	1/55 (1.8%)	2
Gastroesophageal reflux disease	1/55 (1.8%)	2
Gastrointestinal disorders - Other	3/55 (5.5%)	4
Gastrointestinal pain	1/55 (1.8%)	1
Hemorrhoids	1/55 (1.8%)	1
Ileus	1/55 (1.8%)	1
Mucositis oral	4/55 (7.3%)	4
Nausea	20/55 (36.4%)	29
Oral hemorrhage	1/55 (1.8%)	1
Oral pain	2/55 (3.6%)	2
Toothache	1/55 (1.8%)	2
Typhlitis	1/55 (1.8%)	1
Upper gastrointestinal hemorrhage	2/55 (3.6%)	3
Vomiting	13/55 (23.6%)	16
General disorders
Chills	5/55 (9.1%)	5
Edema face	1/55 (1.8%)	2
Edema limbs	5/55 (9.1%)	6
Edema trunk	2/55 (3.6%)	2
Fatigue	22/55 (40%)	34
Fever	9/55 (16.4%)	11
General disorders and administration site conditions - Other	5/55 (9.1%)	5
Infusion related reaction	1/55 (1.8%)	2
Malaise	3/55 (5.5%)	3
Multi-organ failure	1/55 (1.8%)	1
Non-cardiac chest pain	1/55 (1.8%)	1
Pain	5/55 (9.1%)	9
Hepatobiliary disorders
Hepatic hemorrhage	1/55 (1.8%)	1
Infections and infestations
Catheter related infection	2/55 (3.6%)	2
Enterocolitis infectious	1/55 (1.8%)	1
Infections and infestations - Other	3/55 (5.5%)	3
Lung infection	8/55 (14.5%)	9
Mucosal infection	2/55 (3.6%)	2
Sepsis	6/55 (10.9%)	8
Sinusitis	1/55 (1.8%)	1
Skin infection	2/55 (3.6%)	3
Small intestine infection	1/55 (1.8%)	1
Urinary tract infection	1/55 (1.8%)	1
Injury, poisoning and procedural complications
Bruising	2/55 (3.6%)	2
Fall	1/55 (1.8%)	1
Investigations
Activated partial thromboplastin time prolonged	9/55 (16.4%)	10
Alanine aminotransferase increased	15/55 (27.3%)	20
Alkaline phosphatase increased	9/55 (16.4%)	14
Aspartate aminotransferase increased	17/55 (30.9%)	20
Blood bilirubin increased	10/55 (18.2%)	14
Cardiac troponin I increased	1/55 (1.8%)	1
Creatinine increased	11/55 (20%)	16
Electrocardiogram QT corrected interval prolonged	6/55 (10.9%)	9
Hemoglobin increased	1/55 (1.8%)	1
INR increased	9/55 (16.4%)	11
Investigations - Other	3/55 (5.5%)	4
Lymphocyte count decreased	18/55 (32.7%)	26
Lymphocyte count increased	2/55 (3.6%)	2
Neutrophil count decreased	26/55 (47.3%)	43
Platelet count decreased	27/55 (49.1%)	45
Weight gain	1/55 (1.8%)	1
Weight loss	6/55 (10.9%)	11
White blood cell decreased	18/55 (32.7%)	29
Metabolism and nutrition disorders
Acidosis	4/55 (7.3%)	4
Alkalosis	2/55 (3.6%)	2
Anorexia	11/55 (20%)	18
Dehydration	3/55 (5.5%)	5
Hyperglycemia	19/55 (34.5%)	28
Hyperkalemia	7/55 (12.7%)	7
Hypermagnesemia	3/55 (5.5%)	3
Hypernatremia	4/55 (7.3%)	5
Hyperuricemia	6/55 (10.9%)	6
Hypoalbuminemia	21/55 (38.2%)	34
Hypocalcemia	12/55 (21.8%)	17
Hypoglycemia	3/55 (5.5%)	3
Hypokalemia	16/55 (29.1%)	18
Hypomagnesemia	6/55 (10.9%)	11
Hyponatremia	13/55 (23.6%)	19
Hypophosphatemia	6/55 (10.9%)	9
Metabolism and nutrition disorders - Other	2/55 (3.6%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	3/55 (5.5%)	5
Back pain	1/55 (1.8%)	1
Generalized muscle weakness	4/55 (7.3%)	8
Musculoskeletal and connective tissue disorder - Other	2/55 (3.6%)	3
Myalgia	2/55 (3.6%)	2
Neck pain	1/55 (1.8%)	1
Pain in extremity	2/55 (3.6%)	2
Nervous system disorders
Ataxia	1/55 (1.8%)	1
Dizziness	5/55 (9.1%)	7
Dysgeusia	2/55 (3.6%)	2
Headache	12/55 (21.8%)	17
Hydrocephalus	1/55 (1.8%)	1
Intracranial hemorrhage	1/55 (1.8%)	1
Lethargy	1/55 (1.8%)	1
Nervous system disorders - Other	1/55 (1.8%)	1
Paresthesia	1/55 (1.8%)	1
Peripheral sensory neuropathy	3/55 (5.5%)	3
Sinus pain	1/55 (1.8%)	1
Somnolence	1/55 (1.8%)	1
Syncope	2/55 (3.6%)	2
Tremor	1/55 (1.8%)	1
Psychiatric disorders
Agitation	1/55 (1.8%)	1
Anxiety	5/55 (9.1%)	6
Confusion	1/55 (1.8%)	1
Delirium	1/55 (1.8%)	2
Depression	3/55 (5.5%)	5
Insomnia	3/55 (5.5%)	5
Renal and urinary disorders
Acute kidney injury	7/55 (12.7%)	9
Chronic kidney disease	2/55 (3.6%)	4
Hematuria	4/55 (7.3%)	6
Proteinuria	7/55 (12.7%)	9
Urinary frequency	1/55 (1.8%)	1
Urinary incontinence	1/55 (1.8%)	1
Urinary tract pain	1/55 (1.8%)	1
Reproductive system and breast disorders
Genital edema	1/55 (1.8%)	1
Menorrhagia	1/55 (1.8%)	1
Perineal pain	1/55 (1.8%)	1
Vaginal hemorrhage	1/55 (1.8%)	2
Respiratory, thoracic and mediastinal disorders
Cough	7/55 (12.7%)	7
Dyspnea	11/55 (20%)	13
Epistaxis	1/55 (1.8%)	1
Hypoxia	3/55 (5.5%)	4
Nasal congestion	1/55 (1.8%)	1
Pharyngolaryngeal pain	1/55 (1.8%)	1
Pleural effusion	4/55 (7.3%)	5
Pleuritic pain	1/55 (1.8%)	1
Pneumonitis	2/55 (3.6%)	2
Respiratory failure	5/55 (9.1%)	5
Respiratory, thoracic and mediastinal disorders - Other	3/55 (5.5%)	3
Sore throat	3/55 (5.5%)	3
Wheezing	1/55 (1.8%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/55 (5.5%)	3
Dry skin	2/55 (3.6%)	2
Erythema multiforme	1/55 (1.8%)	2
Palmar-plantar erythrodysesthesia syndrome	1/55 (1.8%)	1
Pruritus	1/55 (1.8%)	1
Purpura	2/55 (3.6%)	3
Rash maculo-papular	8/55 (14.5%)	12
Skin and subcutaneous tissue disorders - Other	4/55 (7.3%)	7
Skin ulceration	1/55 (1.8%)	1
Vascular disorders
Flushing	1/55 (1.8%)	1
Hypertension	5/55 (9.1%)	7
Hypotension	9/55 (16.4%)	12
Peripheral ischemia	1/55 (1.8%)	1
Vascular disorders - Other	1/55 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)
	Affected / at Risk (%)	# Events
Total	51/55 (92.7%)
Blood and lymphatic system disorders
Anemia	49/55 (89.1%)	327
Blood and lymphatic system disorders - Other	2/55 (3.6%)	3
Disseminated intravascular coagulation	6/55 (10.9%)	7
Febrile neutropenia	31/55 (56.4%)	63
Leukocytosis	3/55 (5.5%)	3
Lymph node pain	2/55 (3.6%)	3
Cardiac disorders
Atrioventricular block first degree	1/55 (1.8%)	3
Cardiac disorders - Other	3/55 (5.5%)	4
Chest pain - cardiac	2/55 (3.6%)	2
Heart failure	3/55 (5.5%)	4
Left ventricular systolic dysfunction	3/55 (5.5%)	7
Mitral valve disease	1/55 (1.8%)	3
Palpitations	5/55 (9.1%)	6
Sinus bradycardia	3/55 (5.5%)	3
Sinus tachycardia	16/55 (29.1%)	38
Ventricular arrhythmia	2/55 (3.6%)	2
Ear and labyrinth disorders
Ear and labyrinth disorders - Other	1/55 (1.8%)	1
Endocrine disorders
Hypothyroidism	1/55 (1.8%)	1
Eye disorders
Blurred vision	6/55 (10.9%)	10
Conjunctivitis	3/55 (5.5%)	3
Eye disorders - Other	3/55 (5.5%)	4
Eye pain	2/55 (3.6%)	2
Floaters	1/55 (1.8%)	1
Keratitis	2/55 (3.6%)	2
Photophobia	2/55 (3.6%)	2
Retinal vascular disorder	1/55 (1.8%)	1
Gastrointestinal disorders
Abdominal distension	2/55 (3.6%)	3
Abdominal pain	12/55 (21.8%)	22
Anal hemorrhage	2/55 (3.6%)	3
Anal pain	2/55 (3.6%)	2
Ascites	2/55 (3.6%)	3
Bloating	1/55 (1.8%)	1
Constipation	30/55 (54.5%)	61
Dental caries	2/55 (3.6%)	2
Diarrhea	44/55 (80%)	91
Dyspepsia	3/55 (5.5%)	4
Dysphagia	5/55 (9.1%)	8
Enterocolitis	1/55 (1.8%)	1
Fecal incontinence	1/55 (1.8%)	1
Flatulence	2/55 (3.6%)	4
Gastric hemorrhage	1/55 (1.8%)	1
Gastritis	1/55 (1.8%)	1
Gastroesophageal reflux disease	9/55 (16.4%)	21
Gastrointestinal disorders - Other	8/55 (14.5%)	15
Gastrointestinal pain	1/55 (1.8%)	6
Gingival pain	2/55 (3.6%)	3
Hemorrhoids	1/55 (1.8%)	2
Ileus	1/55 (1.8%)	1
Lower gastrointestinal hemorrhage	1/55 (1.8%)	1
Mucositis oral	24/55 (43.6%)	53
Nausea	47/55 (85.5%)	165
Oral hemorrhage	2/55 (3.6%)	2
Oral pain	8/55 (14.5%)	16
Rectal hemorrhage	1/55 (1.8%)	1
Rectal pain	4/55 (7.3%)	6
Rectal ulcer	1/55 (1.8%)	2
Stomach pain	2/55 (3.6%)	4
Tooth discoloration	1/55 (1.8%)	1
Toothache	3/55 (5.5%)	5
Typhlitis	2/55 (3.6%)	2
Vomiting	37/55 (67.3%)	84
General disorders
Chills	12/55 (21.8%)	18
Edema face	3/55 (5.5%)	4
Edema limbs	19/55 (34.5%)	30
Edema trunk	1/55 (1.8%)	1
Facial pain	1/55 (1.8%)	1
Fatigue	47/55 (85.5%)	206
Fever	26/55 (47.3%)	46
General disorders and administration site conditions - Other	10/55 (18.2%)	18
Infusion related reaction	4/55 (7.3%)	5
Injection site reaction	1/55 (1.8%)	1
Localized edema	3/55 (5.5%)	6
Malaise	3/55 (5.5%)	5
Non-cardiac chest pain	7/55 (12.7%)	11
Pain	5/55 (9.1%)	11
Hepatobiliary disorders
Cholecystitis	1/55 (1.8%)	1
Infections and infestations
Anorectal infection	1/55 (1.8%)	1
Catheter related infection	3/55 (5.5%)	3
Device related infection	4/55 (7.3%)	4
Enterocolitis infectious	1/55 (1.8%)	1
Infections and infestations - Other	14/55 (25.5%)	24
Lip infection	2/55 (3.6%)	3
Lung infection	12/55 (21.8%)	25
Lymph gland infection	1/55 (1.8%)	2
Mucosal infection	2/55 (3.6%)	2
Paronychia	1/55 (1.8%)	1
Pharyngitis	1/55 (1.8%)	1
Sepsis	3/55 (5.5%)	4
Sinusitis	3/55 (5.5%)	4
Skin infection	6/55 (10.9%)	6
Soft tissue infection	1/55 (1.8%)	1
Tooth infection	1/55 (1.8%)	1
Upper respiratory infection	3/55 (5.5%)	3
Urinary tract infection	3/55 (5.5%)	4
Vaginal infection	2/55 (3.6%)	3
Vulval infection	1/55 (1.8%)	1
Wound infection	1/55 (1.8%)	2
Injury, poisoning and procedural complications
Bruising	10/55 (18.2%)	12
Fall	3/55 (5.5%)	3
Injury, poisoning and procedural complications - Other	1/55 (1.8%)	1
Postoperative hemorrhage	1/55 (1.8%)	1
Investigations
Activated partial thromboplastin time prolonged	18/55 (32.7%)	31
Alanine aminotransferase increased	41/55 (74.5%)	107
Alkaline phosphatase increased	21/55 (38.2%)	50
Aspartate aminotransferase increased	30/55 (54.5%)	72
Blood bilirubin increased	19/55 (34.5%)	49
Cardiac troponin I increased	1/55 (1.8%)	1
Cholesterol high	1/55 (1.8%)	1
Creatinine increased	10/55 (18.2%)	25
Ejection fraction decreased	1/55 (1.8%)	1
Electrocardiogram QT corrected interval prolonged	15/55 (27.3%)	59
Fibrinogen decreased	2/55 (3.6%)	2
INR increased	22/55 (40%)	49
Investigations - Other	1/55 (1.8%)	3
Lymphocyte count decreased	32/55 (58.2%)	134
Lymphocyte count increased	8/55 (14.5%)	11
Neutrophil count decreased	51/55 (92.7%)	261
Platelet count decreased	51/55 (92.7%)	299
Weight gain	3/55 (5.5%)	10
Weight loss	12/55 (21.8%)	37
White blood cell decreased	40/55 (72.7%)	173
Metabolism and nutrition disorders
Anorexia	27/55 (49.1%)	57
Dehydration	1/55 (1.8%)	1
Hypercalcemia	5/55 (9.1%)	8
Hyperglycemia	40/55 (72.7%)	175
Hyperkalemia	10/55 (18.2%)	17
Hypermagnesemia	7/55 (12.7%)	7
Hypernatremia	5/55 (9.1%)	7
Hypertriglyceridemia	1/55 (1.8%)	2
Hyperuricemia	14/55 (25.5%)	23
Hypoalbuminemia	38/55 (69.1%)	133
Hypocalcemia	36/55 (65.5%)	87
Hypoglycemia	8/55 (14.5%)	11
Hypokalemia	30/55 (54.5%)	64
Hypomagnesemia	14/55 (25.5%)	35
Hyponatremia	30/55 (54.5%)	76
Hypophosphatemia	20/55 (36.4%)	25
Metabolism and nutrition disorders - Other	4/55 (7.3%)	36
Tumor lysis syndrome	1/55 (1.8%)	1
Musculoskeletal and connective tissue disorders
Abdominal soft tissue necrosis	1/55 (1.8%)	1
Arthralgia	6/55 (10.9%)	10
Arthritis	3/55 (5.5%)	4
Avascular necrosis	1/55 (1.8%)	2
Back pain	15/55 (27.3%)	26
Bone pain	5/55 (9.1%)	8
Buttock pain	3/55 (5.5%)	3
Chest wall pain	2/55 (3.6%)	2
Flank pain	1/55 (1.8%)	1
Generalized muscle weakness	10/55 (18.2%)	16
Muscle weakness lower limb	1/55 (1.8%)	1
Musculoskeletal and connective tissue disorder - Other	5/55 (9.1%)	14
Myalgia	10/55 (18.2%)	16
Neck pain	4/55 (7.3%)	4
Pain in extremity	8/55 (14.5%)	14
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1/55 (1.8%)	1
Nervous system disorders
Akathisia	1/55 (1.8%)	1
Amnesia	2/55 (3.6%)	2
Ataxia	1/55 (1.8%)	2
Concentration impairment	1/55 (1.8%)	1
Dizziness	15/55 (27.3%)	19
Dysgeusia	5/55 (9.1%)	7
Headache	31/55 (56.4%)	88
Lethargy	2/55 (3.6%)	2
Memory impairment	1/55 (1.8%)	1
Nervous system disorders - Other	1/55 (1.8%)	1
Peripheral motor neuropathy	1/55 (1.8%)	1
Peripheral sensory neuropathy	4/55 (7.3%)	8
Tremor	1/55 (1.8%)	4
Psychiatric disorders
Anxiety	13/55 (23.6%)	30
Confusion	1/55 (1.8%)	1
Delirium	1/55 (1.8%)	1
Depression	11/55 (20%)	24
Hallucinations	1/55 (1.8%)	1
Insomnia	15/55 (27.3%)	32
Renal and urinary disorders
Acute kidney injury	1/55 (1.8%)	1
Chronic kidney disease	5/55 (9.1%)	8
Hematuria	4/55 (7.3%)	6
Proteinuria	9/55 (16.4%)	13
Renal and urinary disorders - Other	1/55 (1.8%)	1
Urinary frequency	2/55 (3.6%)	2
Reproductive system and breast disorders
Breast pain	1/55 (1.8%)	1
Genital edema	1/55 (1.8%)	1
Menorrhagia	3/55 (5.5%)	8
Reproductive system and breast disorders - Other	3/55 (5.5%)	4
Vaginal discharge	1/55 (1.8%)	1
Vaginal hemorrhage	2/55 (3.6%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/55 (7.3%)	4
Apnea	1/55 (1.8%)	1
Aspiration	1/55 (1.8%)	1
Atelectasis	3/55 (5.5%)	3
Bronchopulmonary hemorrhage	2/55 (3.6%)	3
Cough	22/55 (40%)	40
Dyspnea	26/55 (47.3%)	52
Epistaxis	8/55 (14.5%)	10
Hypoxia	5/55 (9.1%)	7
Laryngeal inflammation	1/55 (1.8%)	1
Nasal congestion	9/55 (16.4%)	14
Pharyngolaryngeal pain	2/55 (3.6%)	3
Pleural effusion	13/55 (23.6%)	21
Pleuritic pain	3/55 (5.5%)	5
Pneumonitis	2/55 (3.6%)	6
Productive cough	3/55 (5.5%)	3
Pulmonary edema	1/55 (1.8%)	2
Respiratory, thoracic and mediastinal disorders - Other	5/55 (9.1%)	11
Sinus disorder	1/55 (1.8%)	1
Sore throat	6/55 (10.9%)	9
Skin and subcutaneous tissue disorders
Alopecia	8/55 (14.5%)	22
Dry skin	5/55 (9.1%)	9
Erythema multiforme	3/55 (5.5%)	4
Hyperhidrosis	2/55 (3.6%)	3
Pain of skin	2/55 (3.6%)	2
Palmar-plantar erythrodysesthesia syndrome	4/55 (7.3%)	12
Periorbital edema	1/55 (1.8%)	1
Photosensitivity	1/55 (1.8%)	1
Pruritus	8/55 (14.5%)	11
Purpura	5/55 (9.1%)	6
Rash acneiform	1/55 (1.8%)	3
Rash maculo-papular	31/55 (56.4%)	79
Scalp pain	1/55 (1.8%)	2
Skin and subcutaneous tissue disorders - Other	18/55 (32.7%)	37
Skin ulceration	3/55 (5.5%)	3
Vascular disorders
Flushing	1/55 (1.8%)	2
Hematoma	5/55 (9.1%)	5
Hypertension	14/55 (25.5%)	32
Hypotension	14/55 (25.5%)	25
Thromboembolic event	2/55 (3.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.