Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01253070
• Collaborator: (none)
• Enrollment: 54
• Locations: 43
• Arm: 1
• Actual Duration (Months): 120.5
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well sorafenib tosylate and chemotherapy work in treating older patients with acute myeloid leukemia (AML). Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Giving sorafenib tosylate and combination chemotherapy may be an effective treatment for AML.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11; Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Acute Promyelocytic Leukemia With PML-RARA; FLT3 Gene Mutation; Therapy-Related Acute Myeloid Leukemia	Procedure: Biopsy; Procedure: Bone Marrow Aspiration; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sorafenib Tosylate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if the 1-year overall survival rate of patients age >= 60 with FLT3-ITD AML treated with a sorafenib (sorafenib tosylate) containing induction and post-remission therapy is significantly higher than the historical 1-year overall survival rate of similar patients who were not treated with sorafenib.

SECONDARY OBJECTIVES:

1. To determine the rates of complete remission (CR), CR with incomplete count recovery (CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy.

2. To determine the overall survival, event-free survival, and remission duration in patients treated on this study.

3. To describe the frequency and severity of adverse events for patients treated on this study.

4. To describe the interaction of pre-treatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

5. To assess FLT3 ligand concentrations and FLT3 plasma inhibitory activity during treatment and determine the relationship to clinical outcomes. (Cancer and Leukemia Group B [CALGB]

1. 1. To describe the interaction of FLT3 mutation type (tyrosine kinase domain [TKD] vs. ITD) and allelic ratio on clinical outcomes. (CALGB 21003) VII. To characterize geriatric assessment measures in the context of a treatment trial for AML defined by: the observed distribution and number of missing values for each measurement. (CALGB 361006) VIII. To identify specific geriatric assessment measures which are independently associated with overall survival (OS), 30-day treatment-related mortality and key quality of life outcomes (number of days hospitalized, number of oncology clinic visits, admission to a nursing facility) in patients receiving induction chemotherapy for AML. (CALGB 361006) IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial factors. (CALGB

OUTLINE:

INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously on days 1-7, and sorafenib tosylate orally (PO) twice daily (BID) on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.

Patients with persistent disease undergo a second remission induction therapy comprising daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and sorafenib tosylate PO BID on days 1-7. Patients who achieve complete response (CR)* proceed to consolidation therapy.

CONSOLIDATION THERAPY: Patients** receive cytarabine IV over 3 hours on days 1-5 and sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with continued CR proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who achieve CR and who are eligible for hematopoietic stem cell transplant (HSCT) are encouraged to enroll in Cancer and Leukemia Group B (CALGB) 100103. Patients in CR who are unable or unwilling to undergo HSCT receive two cycles of remission consolidation therapy.

NOTE: ** Patients in CR/complete remission with incomplete count recovery (CRi) who are unable or unwilling to complete remission consolidation therapy may proceed directly to maintenance therapy after consulting with the CALGB study chair.

After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then yearly for a maximum of 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Incorporating Sorafenib (NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia
• Actual Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Oct 31, 2014
• Actual Study Completion Date: Apr 15, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (daunorubicin, cytarabine, sorafenib tosylate) INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.

Procedure: Biopsy; Undergo biopsy; Other Names: BIOPSY_TYPE Bx ; Procedure: Bone Marrow Aspiration; Undergo bone marrow aspirate; 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: 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; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) Rate [1 year]

   Percentage of patients who were alive at 1 year. The analysis was split between patients with having a FLT3 (FMS-like tyrosine kinase-3) ITD (internal tandem duplication) or TKD (tyrosine kinase domain) mutation. The FLT3 mutation testing at baseline was performed centrally for all patients.

Secondary Outcome Measures

1. OS [Time from registration to death (up to 10 years)]

   OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.

2. Event-free Survival [Time from registration to death or relapse (up to 10 years)]

   Event-free survival (EFS) was defined as the time for registration to failure to achieve CR during induction, relapse or death. Participants without events were censored at date of last follow-up. The median EFS with 95% CI was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unequivocal histologic diagnosis of AML according to World Health Organization (WHO) criteria, EXCLUDING:

• Acute promyelocytic leukemia t(15;17)(q22;q12); promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RARA)

• Acute myeloid leukemia with t(8;21)(q22;q22); runt-related transcription factor 1 (RUNX1-RUNXT1) as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per CALGB 20202

• Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16(p13.1;q22); core-binding factor, beta subunit (CBFB)-myosin, heavy chain 11, smooth muscle (MYH11) as determined by the OSU Molecular Reference Laboratory, per CALGB 20202

• AML patients with an antecedent hematologic disorder are eligible for treatment on this trial provided that they have not received chemotherapy, including lenalidomide, azacitidine or decitabine for their hematologic disorder; patients with therapy-related AML are eligible if there had been no further exposure to chemotherapy or radiation therapy for > 3 years and their primary malignancy is in remission

• FLT3 mutation (ITD or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202

• No prior chemotherapy for AML with the following exceptions:

• Emergency leukapheresis

• Emergency treatment for hyperleukocytosis with hydroxyurea

• Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)

• Growth factor/cytokine support

• All-trans retinoic acid (ATRA)

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	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
5	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
6	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
7	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
8	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
9	Eastern Maine Medical Center	Bangor	Maine	United States	04401
10	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
11	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
12	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
13	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
14	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
15	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
16	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
17	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
18	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
19	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
20	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
21	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
22	Munson Medical Center	Traverse City	Michigan	United States	49684
23	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
24	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
25	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
26	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
27	Northwell Health NCORP	Lake Success	New York	United States	11042
28	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
29	North Shore University Hospital	Manhasset	New York	United States	11030
30	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
31	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
32	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
33	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
34	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
35	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
36	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
37	Cancer Care Associates-Norman	Norman	Oklahoma	United States	73071
38	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
39	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
40	Roper Hospital	Charleston	South Carolina	United States	29401
41	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
42	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
43	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Geoffrey L Uy, 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: NCT01253070
• Other Study ID Numbers: NCI-2011-02618; NCI-2011-02618; CDR0000689593; CALGB-11001; CALGB-11001; U10CA180821; U10CA031946
• First Posted: Dec 3, 2010
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Cytarabine; Sorafenib; Daunorubicin

Study Results

Participant Flow

Recruitment Details	A total of 54 participants were recruited from April 2011 to August 2013.

Arm/Group Title	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Period Title: Overall Study
STARTED	54
COMPLETED	54
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Overall Participants	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.4
Sex: Female, Male (Count of Participants)
Female	24 44.4%
Male	30 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 3.7%
Not Hispanic or Latino	47 87%
Unknown or Not Reported	5 9.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.9%
White	51 94.4%
More than one race	0 0%
Unknown or Not Reported	2 3.7%
Region of Enrollment (participants) [Number]
United States	54 100%
FLT3 Mutation (participants) [Number]
ITD	39 72.2%
TKD	15 27.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) Rate
Description	Percentage of patients who were alive at 1 year. The analysis was split between patients with having a FLT3 (FMS-like tyrosine kinase-3) ITD (internal tandem duplication) or TKD (tyrosine kinase domain) mutation. The FLT3 mutation testing at baseline was performed centrally for all patients.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Three participants withdrew consent to protocol treatment and follow-up prior to 1 year post registration (2 ITD; 1 TKD). These participants have been excluded from the primary endpoint analysis.

Arm/Group Title	ITD Mutated Participants	TKD Mutated Participants
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Measure Participants	37	14
Number (95% Confidence Interval) [percentage of participants]	62 114.8%	71 NaN

2. Secondary Outcome

Title	OS
Description	OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.
Time Frame	Time from registration to death (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ITD Mutated Participants	TKD Mutated Participants
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Measure Participants	39	15
Median (95% Confidence Interval) [months]	15	16.2

3. Secondary Outcome

Title	Event-free Survival
Description	Event-free survival (EFS) was defined as the time for registration to failure to achieve CR during induction, relapse or death. Participants without events were censored at date of last follow-up. The median EFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	Time from registration to death or relapse (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ITD Mutated Participants	TKD Mutated Participants
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Measure Participants	39	15
Median (95% Confidence Interval) [months]	8.8	7.8

Adverse Events

Adverse Event Reporting Description	At the time of analysis, adverse event data was collected on 50 of 54 participants.
Arm/Group Title	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
Arm/Group Description	INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400 mg orally every 12 hours on days 1-7. CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28. MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
All Cause Mortality
	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	21/50 (42%)
Blood and lymphatic system disorders
Anemia	20/50 (40%)	24
Blood and lymphatic system disorders - Other	2/50 (4%)	2
Disseminated intravascular coagulation	2/50 (4%)	2
Febrile neutropenia	13/50 (26%)	15
Leukocytosis	1/50 (2%)	1
Cardiac disorders
Atrial fibrillation	5/50 (10%)	5
Atrial flutter	1/50 (2%)	1
Atrioventricular block first degree	1/50 (2%)	1
Cardiac arrest	2/50 (4%)	2
Cardiac disorders - Other	1/50 (2%)	1
Chest pain - cardiac	1/50 (2%)	1
Heart failure	2/50 (4%)	2
Left ventricular systolic dysfunction	3/50 (6%)	3
Pericarditis	1/50 (2%)	1
Sinus bradycardia	2/50 (4%)	2
Sinus tachycardia	4/50 (8%)	4
Supraventricular tachycardia	2/50 (4%)	2
Ventricular arrhythmia	2/50 (4%)	2
Ventricular tachycardia	1/50 (2%)	1
Ear and labyrinth disorders
Hearing impaired	1/50 (2%)	1
Endocrine disorders
Hypothyroidism	1/50 (2%)	1
Eye disorders
Blurred vision	2/50 (4%)	2
Dry eye	1/50 (2%)	1
Eye disorders - Other	1/50 (2%)	1
Gastrointestinal disorders
Abdominal pain	6/50 (12%)	6
Constipation	4/50 (8%)	4
Diarrhea	14/50 (28%)	14
Gastrointestinal disorders - Other	2/50 (4%)	2
Mucositis oral	7/50 (14%)	7
Nausea	7/50 (14%)	9
Oral hemorrhage	1/50 (2%)	1
Oral pain	1/50 (2%)	1
Rectal hemorrhage	1/50 (2%)	1
Rectal pain	1/50 (2%)	1
Small intestinal obstruction	1/50 (2%)	1
Vomiting	3/50 (6%)	5
General disorders
Chills	1/50 (2%)	1
Edema limbs	7/50 (14%)	9
Fatigue	11/50 (22%)	13
Fever	1/50 (2%)	1
Localized edema	1/50 (2%)	1
Multi-organ failure	1/50 (2%)	1
Non-cardiac chest pain	1/50 (2%)	1
Pain	2/50 (4%)	7
Immune system disorders
Allergic reaction	1/50 (2%)	2
Infections and infestations
Bone infection	1/50 (2%)	2
Enterocolitis infectious	1/50 (2%)	1
Infections and infestations - Other	1/50 (2%)	1
Laryngitis	1/50 (2%)	1
Lip infection	1/50 (2%)	1
Lung infection	8/50 (16%)	10
Sepsis	6/50 (12%)	7
Urinary tract infection	4/50 (8%)	4
Injury, poisoning and procedural complications
Bruising	1/50 (2%)	1
Investigations
Activated partial thromboplastin time prolonged	3/50 (6%)	3
Alanine aminotransferase increased	8/50 (16%)	8
Alkaline phosphatase increased	6/50 (12%)	7
Aspartate aminotransferase increased	11/50 (22%)	11
Blood bilirubin increased	8/50 (16%)	8
Creatinine increased	5/50 (10%)	5
Ejection fraction decreased	2/50 (4%)	2
Electrocardiogram QT corrected interval prolonged	1/50 (2%)	1
INR increased	4/50 (8%)	6
Investigations - Other	2/50 (4%)	4
Lymphocyte count decreased	8/50 (16%)	10
Neutrophil count decreased	19/50 (38%)	22
Platelet count decreased	20/50 (40%)	23
Urine output decreased	1/50 (2%)	1
Weight gain	1/50 (2%)	1
Weight loss	2/50 (4%)	2
White blood cell decreased	14/50 (28%)	15
Metabolism and nutrition disorders
Acidosis	3/50 (6%)	3
Alkalosis	1/50 (2%)	1
Anorexia	8/50 (16%)	9
Hypercalcemia	3/50 (6%)	3
Hyperglycemia	11/50 (22%)	11
Hyperkalemia	3/50 (6%)	3
Hypermagnesemia	2/50 (4%)	2
Hypernatremia	2/50 (4%)	2
Hyperuricemia	2/50 (4%)	3
Hypoalbuminemia	13/50 (26%)	16
Hypocalcemia	11/50 (22%)	11
Hypoglycemia	2/50 (4%)	2
Hypokalemia	10/50 (20%)	10
Hypomagnesemia	5/50 (10%)	5
Hyponatremia	11/50 (22%)	13
Hypophosphatemia	8/50 (16%)	11
Metabolism and nutrition disorders - Other	1/50 (2%)	1
Musculoskeletal and connective tissue disorders
Back pain	4/50 (8%)	6
Chest wall pain	1/50 (2%)	1
Flank pain	1/50 (2%)	1
Generalized muscle weakness	5/50 (10%)	5
Muscle weakness right-sided	2/50 (4%)	2
Osteoporosis	1/50 (2%)	1
Pain in extremity	1/50 (2%)	1
Nervous system disorders
Ataxia	1/50 (2%)	1
Depressed level of consciousness	1/50 (2%)	1
Dizziness	1/50 (2%)	1
Dysarthria	1/50 (2%)	1
Headache	2/50 (4%)	2
Lethargy	1/50 (2%)	1
Nervous system disorders - Other	1/50 (2%)	1
Peripheral sensory neuropathy	1/50 (2%)	1
Reversible posterior leukoencephalopathy syndrome	1/50 (2%)	1
Seizure	1/50 (2%)	1
Transient ischemic attacks	1/50 (2%)	1
Psychiatric disorders
Anxiety	2/50 (4%)	2
Confusion	4/50 (8%)	4
Insomnia	2/50 (4%)	2
Renal and urinary disorders
Acute kidney injury	3/50 (6%)	3
Chronic kidney disease	1/50 (2%)	1
Hematuria	3/50 (6%)	3
Proteinuria	2/50 (4%)	2
Renal calculi	1/50 (2%)	1
Urinary incontinence	2/50 (4%)	2
Urinary retention	1/50 (2%)	1
Urinary tract pain	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/50 (2%)	1
Cough	4/50 (8%)	4
Dyspnea	5/50 (10%)	5
Hiccups	1/50 (2%)	1
Hypoxia	3/50 (6%)	3
Nasal congestion	1/50 (2%)	1
Pleural effusion	3/50 (6%)	3
Pulmonary edema	4/50 (8%)	4
Pulmonary hypertension	1/50 (2%)	1
Respiratory failure	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders - Other	2/50 (4%)	2
Sore throat	1/50 (2%)	1
Wheezing	2/50 (4%)	2
Skin and subcutaneous tissue disorders
Alopecia	1/50 (2%)	1
Dry skin	1/50 (2%)	1
Erythema multiforme	2/50 (4%)	2
Hyperhidrosis	1/50 (2%)	1
Pain of skin	1/50 (2%)	1
Palmar-plantar erythrodysesthesia syndrome	1/50 (2%)	1
Pruritus	3/50 (6%)	3
Rash maculo-papular	10/50 (20%)	13
Skin and subcutaneous tissue disorders - Other	2/50 (4%)	3
Skin induration	1/50 (2%)	1
Skin ulceration	1/50 (2%)	1
Vascular disorders
Hematoma	1/50 (2%)	1
Hypertension	4/50 (8%)	4
Hypotension	5/50 (10%)	6
Thromboembolic event	2/50 (4%)	3
Vascular disorders - Other	2/50 (4%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Daunorubicin, Cytarabine, Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	42/50 (84%)
Blood and lymphatic system disorders
Anemia	41/50 (82%)	134
Blood and lymphatic system disorders - Other	1/50 (2%)	7
Disseminated intravascular coagulation	5/50 (10%)	6
Febrile neutropenia	27/50 (54%)	37
Lymph node pain	1/50 (2%)	1
Cardiac disorders
Atrial fibrillation	3/50 (6%)	8
Chest pain - cardiac	1/50 (2%)	1
Mitral valve disease	1/50 (2%)	1
Palpitations	2/50 (4%)	2
Pericardial effusion	1/50 (2%)	1
Sinus bradycardia	6/50 (12%)	7
Sinus tachycardia	2/50 (4%)	3
Ventricular arrhythmia	1/50 (2%)	1
Ear and labyrinth disorders
Ear pain	3/50 (6%)	3
Vertigo	1/50 (2%)	1
Endocrine disorders
Hypothyroidism	3/50 (6%)	3
Eye disorders
Blurred vision	4/50 (8%)	5
Conjunctivitis	2/50 (4%)	4
Dry eye	1/50 (2%)	1
Eye disorders - Other	2/50 (4%)	2
Vitreous hemorrhage	1/50 (2%)	1
Gastrointestinal disorders
Abdominal distension	3/50 (6%)	3
Abdominal pain	13/50 (26%)	18
Anal ulcer	1/50 (2%)	1
Colitis	2/50 (4%)	3
Constipation	20/50 (40%)	25
Dental caries	1/50 (2%)	1
Diarrhea	35/50 (70%)	81
Dry mouth	4/50 (8%)	6
Dyspepsia	4/50 (8%)	5
Dysphagia	1/50 (2%)	1
Enterocolitis	1/50 (2%)	1
Esophagitis	1/50 (2%)	1
Flatulence	4/50 (8%)	8
Gastritis	2/50 (4%)	4
Gastroesophageal reflux disease	5/50 (10%)	7
Gastrointestinal disorders - Other	2/50 (4%)	2
Hemorrhoidal hemorrhage	2/50 (4%)	2
Hemorrhoids	6/50 (12%)	7
Lower gastrointestinal hemorrhage	1/50 (2%)	1
Mucositis oral	22/50 (44%)	31
Nausea	30/50 (60%)	58
Oral hemorrhage	3/50 (6%)	3
Oral pain	4/50 (8%)	5
Rectal pain	2/50 (4%)	3
Stomach pain	1/50 (2%)	1
Vomiting	12/50 (24%)	18
General disorders
Chills	12/50 (24%)	14
Edema face	3/50 (6%)	3
Edema limbs	22/50 (44%)	37
Facial pain	1/50 (2%)	1
Fatigue	31/50 (62%)	77
Fever	12/50 (24%)	14
General disorders and administration site conditions - Other	2/50 (4%)	4
Infusion related reaction	2/50 (4%)	2
Malaise	3/50 (6%)	3
Non-cardiac chest pain	1/50 (2%)	1
Pain	8/50 (16%)	11
Hepatobiliary disorders
Hepatobiliary disorders - Other	1/50 (2%)	1
Infections and infestations
Bladder infection	1/50 (2%)	1
Bone infection	1/50 (2%)	2
Catheter related infection	5/50 (10%)	5
Infections and infestations - Other	8/50 (16%)	9
Lip infection	2/50 (4%)	2
Lung infection	3/50 (6%)	5
Pharyngitis	1/50 (2%)	1
Sepsis	3/50 (6%)	3
Sinusitis	2/50 (4%)	2
Skin infection	2/50 (4%)	2
Small intestine infection	1/50 (2%)	2
Upper respiratory infection	2/50 (4%)	2
Urinary tract infection	5/50 (10%)	6
Injury, poisoning and procedural complications
Bruising	7/50 (14%)	7
Fall	4/50 (8%)	4
Investigations
Activated partial thromboplastin time prolonged	7/50 (14%)	10
Alanine aminotransferase increased	26/50 (52%)	66
Alkaline phosphatase increased	17/50 (34%)	28
Aspartate aminotransferase increased	23/50 (46%)	52
Blood bilirubin increased	25/50 (50%)	49
Cholesterol high	2/50 (4%)	2
Creatinine increased	9/50 (18%)	19
Electrocardiogram QT corrected interval prolonged	1/50 (2%)	1
INR increased	11/50 (22%)	22
Investigations - Other	2/50 (4%)	4
Lipase increased	1/50 (2%)	1
Lymphocyte count decreased	21/50 (42%)	68
Neutrophil count decreased	42/50 (84%)	97
Platelet count decreased	42/50 (84%)	133
Serum amylase increased	1/50 (2%)	1
Weight loss	7/50 (14%)	11
White blood cell decreased	30/50 (60%)	71
Metabolism and nutrition disorders
Anorexia	22/50 (44%)	38
Dehydration	3/50 (6%)	6
Hypercalcemia	4/50 (8%)	8
Hyperglycemia	27/50 (54%)	69
Hyperkalemia	5/50 (10%)	5
Hypermagnesemia	6/50 (12%)	6
Hypernatremia	2/50 (4%)	2
Hypertriglyceridemia	3/50 (6%)	3
Hyperuricemia	2/50 (4%)	3
Hypoalbuminemia	34/50 (68%)	67
Hypocalcemia	24/50 (48%)	36
Hypoglycemia	2/50 (4%)	3
Hypokalemia	24/50 (48%)	37
Hypomagnesemia	12/50 (24%)	20
Hyponatremia	24/50 (48%)	40
Hypophosphatemia	22/50 (44%)	31
Metabolism and nutrition disorders - Other	3/50 (6%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	5/50 (10%)	6
Back pain	5/50 (10%)	15
Bone pain	1/50 (2%)	6
Chest wall pain	1/50 (2%)	1
Generalized muscle weakness	7/50 (14%)	8
Joint effusion	1/50 (2%)	1
Muscle weakness right-sided	2/50 (4%)	2
Musculoskeletal and connective tissue disorder - Other	3/50 (6%)	4
Myalgia	3/50 (6%)	3
Neck pain	1/50 (2%)	1
Osteoporosis	1/50 (2%)	1
Pain in extremity	5/50 (10%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1/50 (2%)	2
Nervous system disorders
Dizziness	12/50 (24%)	15
Dysgeusia	3/50 (6%)	3
Headache	16/50 (32%)	20
Lethargy	1/50 (2%)	1
Memory impairment	1/50 (2%)	1
Nervous system disorders - Other	2/50 (4%)	2
Neuralgia	1/50 (2%)	1
Peripheral sensory neuropathy	3/50 (6%)	12
Phantom pain	1/50 (2%)	1
Sinus pain	1/50 (2%)	1
Syncope	1/50 (2%)	1
Transient ischemic attacks	2/50 (4%)	2
Tremor	2/50 (4%)	2
Psychiatric disorders
Anxiety	9/50 (18%)	10
Confusion	3/50 (6%)	3
Depression	6/50 (12%)	6
Hallucinations	2/50 (4%)	2
Insomnia	9/50 (18%)	14
Personality change	1/50 (2%)	2
Renal and urinary disorders
Acute kidney injury	1/50 (2%)	1
Chronic kidney disease	2/50 (4%)	2
Hematuria	4/50 (8%)	9
Proteinuria	3/50 (6%)	8
Renal and urinary disorders - Other	3/50 (6%)	10
Urinary frequency	5/50 (10%)	9
Urinary incontinence	2/50 (4%)	2
Reproductive system and breast disorders
Vaginal hemorrhage	3/50 (6%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/50 (2%)	1
Atelectasis	2/50 (4%)	2
Cough	13/50 (26%)	21
Dyspnea	18/50 (36%)	25
Epistaxis	12/50 (24%)	14
Hiccups	1/50 (2%)	1
Hoarseness	1/50 (2%)	1
Hypoxia	2/50 (4%)	2
Laryngeal hemorrhage	1/50 (2%)	1
Nasal congestion	5/50 (10%)	6
Pharyngeal hemorrhage	1/50 (2%)	1
Pleural effusion	2/50 (4%)	2
Postnasal drip	1/50 (2%)	1
Productive cough	1/50 (2%)	1
Pulmonary edema	4/50 (8%)	4
Respiratory, thoracic and mediastinal disorders - Other	3/50 (6%)	9
Sore throat	3/50 (6%)	3
Wheezing	1/50 (2%)	1
Skin and subcutaneous tissue disorders
Alopecia	8/50 (16%)	12
Bullous dermatitis	3/50 (6%)	4
Dry skin	8/50 (16%)	19
Erythema multiforme	4/50 (8%)	5
Hyperhidrosis	3/50 (6%)	5
Pain of skin	2/50 (4%)	3
Palmar-plantar erythrodysesthesia syndrome	9/50 (18%)	18
Periorbital edema	1/50 (2%)	1
Pruritus	8/50 (16%)	10
Purpura	3/50 (6%)	3
Rash acneiform	1/50 (2%)	2
Rash maculo-papular	30/50 (60%)	63
Scalp pain	1/50 (2%)	1
Skin and subcutaneous tissue disorders - Other	11/50 (22%)	26
Skin ulceration	2/50 (4%)	2
Urticaria	1/50 (2%)	1
Vascular disorders
Flushing	1/50 (2%)	1
Hematoma	1/50 (2%)	1
Hot flashes	2/50 (4%)	5
Hypertension	17/50 (34%)	30
Hypotension	11/50 (22%)	13
Phlebitis	1/50 (2%)	1
Thromboembolic event	1/50 (2%)	2
Vascular disorders - Other	1/50 (2%)	4

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.