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Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00651261
Recruitment Status : Active, not recruiting
First Posted : April 2, 2008
Results First Posted : February 6, 2017
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Leukemia
Interventions Drug: cytarabine
Drug: daunorubicin
Drug: midostaurin
Other: placebo
Drug: dexamethasone acetate
Enrollment 717
Recruitment Details Between May 2008 and October 2001, 3,277 participants were pre-registered. Of those, 900 participants had a documented FLT3 mutation. 717 participants were enrolled onto this study.
Pre-assignment Details  
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily. Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Period Title: Overall Study
Started 360 357
Completed 69 51
Not Completed 291 306
Reason Not Completed
Adverse Event             32             22
Death             18             18
Withdrawal by Subject             22             40
Induction failure             24             35
Disease progression             58             58
Alternative therapy             109             107
Other disease or participant decisions             23             23
Never treated             5             3
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo Total
Hide Arm/Group Description Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily. Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily. Total of all reporting groups
Overall Number of Baseline Participants 360 357 717
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 360 participants 357 participants 717 participants
47.1
(19 to 59.8)
48.6
(18 to 60.9)
47.9
(18.0 to 60.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 360 participants 357 participants 717 participants
Female
186
  51.7%
212
  59.4%
398
  55.5%
Male
174
  48.3%
145
  40.6%
319
  44.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 360 participants 357 participants 717 participants
Hispanic or Latino
9
   2.5%
7
   2.0%
16
   2.2%
Not Hispanic or Latino
103
  28.6%
107
  30.0%
210
  29.3%
Unknown or Not Reported
248
  68.9%
243
  68.1%
491
  68.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 360 participants 357 participants 717 participants
American Indian or Alaska Native
0
   0.0%
1
   0.3%
1
   0.1%
Asian
8
   2.2%
5
   1.4%
13
   1.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
   2.2%
9
   2.5%
17
   2.4%
White
147
  40.8%
128
  35.9%
275
  38.4%
More than one race
2
   0.6%
1
   0.3%
3
   0.4%
Unknown or Not Reported
195
  54.2%
213
  59.7%
408
  56.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 360 participants 357 participants 717 participants
Canada 4 9 13
United States 117 106 223
Germany 148 157 305
Belgium 3 5 8
France 3 2 5
Netherlands 3 2 5
Australia 0 2 2
Spain 7 15 22
Austria 7 5 12
Italy 61 44 105
Czech Republic 5 6 11
Slovakia 2 2 4
Hungary 0 2 2
FLT3 mutational subtype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 360 participants 357 participants 717 participants
TKD (No ITD) 81 81 162
ITD Allelic ratio <0.7 171 170 341
ITD Allelic ratio >=0.7 108 106 214
[1]
Measure Description: Mutations in the gene encoding the trans-membrane tyrosine kinase FLT3. FLT3 internal tandem duplications (ITD) mutation which results in a duplication between 3 and greater than 100 amino acids most commonly located in the juxtamembrane region. Tyrosine kinase domain (TKD) point mutations are the remainder of those with FLT3 mutations. FLT3 testing was done centrally.
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the time interval from randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time Frame Duration of study (Up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description:
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Overall Number of Participants Analyzed 360 357
Median (95% Confidence Interval)
Unit of Measure: months
74.7 [1] 
(31.5 to NA)
25.6
(18.6 to 42.9)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method 1-sided stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.63 to 0.96
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event- Free Survival
Hide Description

Event free survival (EFS) was defined as the time from randomization until the earliest qualifying event, including: failure to obtain a CR on or before 60 days of initiation of protocol therapy; relapse; or death from any cause. Patients alive and event free at the time of analysis were censored on the date of last clinical assessment. The median EFS with 95% CI was estimated using the Kaplan-Meier method.

Due to a higher than expected transplant rate, EFS was promoted to be a key secondary endpoint.

Time Frame Duration of study (Up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description:
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Overall Number of Participants Analyzed 360 357
Median (95% Confidence Interval)
Unit of Measure: months
8.2
(5.4 to 10.7)
3.0
(1.9 to 5.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method 1-sided stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.66 to 0.93
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant
Hide Description Overall survival (OS) was defined as the time interval from randomization to death from any cause. Any participants who received a stem cell transplant were censored at the time of transplant. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time Frame Duration of study (Up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description:
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Overall Number of Participants Analyzed 360 357
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(27.4 to NA)
[1]
The median overall survival with censoring for transplant has not been reached
4.Secondary Outcome
Title Complete Response Rate
Hide Description Percentage of participants who achieved a complete response (CR). A CR was defined as normalization of blood counts and a marrow showing less than 5% blasts occurring on or before day 60.
Time Frame Induction therapy (up to 60 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description:
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Overall Number of Participants Analyzed 360 357
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
59
(54 to 64)
54
(48 to 59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Disease-free Survival (DFS)
Hide Description Disease free survival (DFS) is defined as the time from documentation of first CR at any time to the first of relapse or death from any cause in participants who achieved a CR.
Time Frame Duration of study (Up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description:
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Overall Number of Participants Analyzed 360 357
Median (95% Confidence Interval)
Unit of Measure: months
26.7 [1] 
(19.4 to NA)
15.5
(11.3 to 23.5)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments [Not Specified]
Method 1-sided stratified log rank
Comments [Not Specified]
6.Secondary Outcome
Title DFS Rate One Year After Completing the Planned Continuation Phase
Hide Description [Not Specified]
Time Frame 30 months
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description 709 participants were evaluated for adverse events.
 
Arm/Group Title Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Hide Arm/Group Description Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily. Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
All-Cause Mortality
Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   157/355 (44.23%)      154/354 (43.50%)    
Blood and lymphatic system disorders     
Blood disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bone marrow hypocellular  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Disseminated intravascular coagulation  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Febrile neutropenia  1  105/355 (29.58%)  144 110/354 (31.07%)  152
Hemoglobin decreased  1  154/355 (43.38%)  237 148/354 (41.81%)  230
Hemolysis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Lymph node pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Lymphatic disorder  1  6/355 (1.69%)  6 4/354 (1.13%)  4
Cardiac disorders     
Arrhythmia  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Asystole  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Atrial fibrillation  1  4/355 (1.13%)  4 6/354 (1.69%)  6
Atrial flutter  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Atrial tachycardia  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Cardiac disorder  1  4/355 (1.13%)  4 6/354 (1.69%)  6
Cardiac pain  1  3/355 (0.85%)  3 1/354 (0.28%)  1
Cardiopulmonary arrest  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Conduction disorder  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Left ventricular dysfunction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Left ventricular failure  1  8/355 (2.25%)  9 7/354 (1.98%)  7
Myocardial ischemia  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Palpitations  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Pericardial effusion  1  4/355 (1.13%)  4 5/354 (1.41%)  5
Pericarditis  1  3/355 (0.85%)  3 0/354 (0.00%)  0
Right ventricular dysfunction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Sinus arrhythmia  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Sinus bradycardia  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Sinus tachycardia  1  17/355 (4.79%)  20 15/354 (4.24%)  20
Supraventricular tachycardia  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Ventricular fibrillation  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Ventricular tachycardia  1  0/355 (0.00%)  0 3/354 (0.85%)  3
Ear and labyrinth disorders     
Ear disorder  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Ear pain  1  2/355 (0.56%)  2 3/354 (0.85%)  3
External ear pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Middle ear inflammation  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Tinnitus  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Endocrine disorders     
Endocrine disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Hyperthyroidism  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Hypothyroidism  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Eye disorders     
Cataract  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Conjunctivitis  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Diplopia  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Dry eye syndrome  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Eye disorder  1  8/355 (2.25%)  9 12/354 (3.39%)  12
Eye pain  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Eyelid function disorder  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Flashing vision  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Keratitis  1  5/355 (1.41%)  6 8/354 (2.26%)  9
Optic nerve edema  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Photophobia  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Retinal detachment  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Scleral disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Vision blurred  1  2/355 (0.56%)  2 4/354 (1.13%)  4
Watering eyes  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Gastrointestinal disorders     
Abdominal distension  1  4/355 (1.13%)  4 2/354 (0.56%)  2
Abdominal pain  1  29/355 (8.17%)  33 28/354 (7.91%)  32
Anal fistula  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Anal hemorrhage  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Anal mucositis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Anal pain  1  7/355 (1.97%)  8 5/354 (1.41%)  5
Anal ulcer  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Ascites  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Colitis  1  9/355 (2.54%)  9 9/354 (2.54%)  9
Colonic hemorrhage  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Colonic perforation  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Constipation  1  16/355 (4.51%)  18 17/354 (4.80%)  18
Diarrhea  1  89/355 (25.07%)  111 89/354 (25.14%)  108
Dry mouth  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Duodenal hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Duodenal necrosis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Dyspepsia  1  10/355 (2.82%)  11 8/354 (2.26%)  8
Dysphagia  1  10/355 (2.82%)  10 10/354 (2.82%)  12
Ear, nose and throat examination abnormal  1  40/355 (11.27%)  52 42/354 (11.86%)  54
Endoscopy small intestine abnormal  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Enteritis  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Esophageal pain  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Esophageal ulcer  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Esophagitis  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Flatulence  1  7/355 (1.97%)  8 5/354 (1.41%)  6
Gastric hemorrhage  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Gastrointestinal disorder  1  10/355 (2.82%)  12 10/354 (2.82%)  10
Gastrointestinal pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Gingival pain  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Hemorrhoidal hemorrhage  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Hemorrhoids  1  11/355 (3.10%)  14 7/354 (1.98%)  7
Ileal hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Ileal necrosis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Ileus  1  2/355 (0.56%)  2 4/354 (1.13%)  4
Intestinal necrosis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Intra-abdominal hemorrhage  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Jejunal necrosis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Lower gastrointestinal hemorrhage  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Mucositis oral  1  23/355 (6.48%)  23 11/354 (3.11%)  13
Nausea  1  98/355 (27.61%)  149 91/354 (25.71%)  126
Oral hemorrhage  1  5/355 (1.41%)  6 10/354 (2.82%)  11
Oral pain  1  5/355 (1.41%)  5 5/354 (1.41%)  6
Periodontal disease  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Proctitis  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Rectal hemorrhage  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Rectal obstruction  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Rectal pain  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Salivary gland disorder  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Stomach pain  1  8/355 (2.25%)  12 9/354 (2.54%)  9
Tooth disorder  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Toothache  1  3/355 (0.85%)  3 4/354 (1.13%)  4
Typhlitis  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Upper gastrointestinal hemorrhage  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Vomiting  1  70/355 (19.72%)  101 65/354 (18.36%)  86
General disorders     
Chest pain  1  6/355 (1.69%)  7 11/354 (3.11%)  12
Chills  1  16/355 (4.51%)  21 16/354 (4.52%)  24
Disease progression  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Edema limbs  1  26/355 (7.32%)  32 21/354 (5.93%)  24
Facial pain  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Fatigue  1  95/355 (26.76%)  136 98/354 (27.68%)  130
Fever  1  34/355 (9.58%)  38 33/354 (9.32%)  38
Flu-like symptoms  1  1/355 (0.28%)  1 1/354 (0.28%)  1
General symptom  1  11/355 (3.10%)  14 15/354 (4.24%)  16
Ill-defined disorder  1  1/355 (0.28%)  1 4/354 (1.13%)  4
Injection site reaction  1  14/355 (3.94%)  17 17/354 (4.80%)  22
Localized edema  1  5/355 (1.41%)  5 9/354 (2.54%)  11
Multi-organ failure  1  4/355 (1.13%)  4 5/354 (1.41%)  5
Pain  1  14/355 (3.94%)  17 18/354 (5.08%)  24
Sudden death  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Visceral edema  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Hepatic failure  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Hepatobiliary disease  1  4/355 (1.13%)  4 1/354 (0.28%)  1
Immune system disorders     
Cytokine release syndrome  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Hypersensitivity  1  7/355 (1.97%)  8 14/354 (3.95%)  15
Immune system disorder  1  3/355 (0.85%)  3 3/354 (0.85%)  4
Infections and infestations     
Abdominal infection  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Anal infection  1  6/355 (1.69%)  9 5/354 (1.41%)  5
Anorectal infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Appendicitis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bladder infection  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Bone infection  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Bronchitis  1  1/355 (0.28%)  1 3/354 (0.85%)  4
Catheter related infection  1  29/355 (8.17%)  39 21/354 (5.93%)  26
Colitis, infectious (e.g., Clostridium difficile)  1  3/355 (0.85%)  3 2/354 (0.56%)  2
Conjunctivitis infective  1  4/355 (1.13%)  4 3/354 (0.85%)  3
Eye infection  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Eye infection intraocular  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Gallbladder infection  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Gingival infection  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Hepatic infection  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Infection  1  30/355 (8.45%)  41 26/354 (7.34%)  33
Infectious colitis  1  8/355 (2.25%)  8 9/354 (2.54%)  10
Joint infection  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Kidney infection  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Lip infection  1  5/355 (1.41%)  5 8/354 (2.26%)  9
Lymph gland infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Mucosal infection  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Nail infection  1  3/355 (0.85%)  3 0/354 (0.00%)  0
Opportunistic infection  1  3/355 (0.85%)  3 1/354 (0.28%)  1
Otitis externa  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Otitis media  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Paranasal sinus infection  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Penile infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pharyngitis  1  3/355 (0.85%)  4 2/354 (0.56%)  2
Phlebitis infective  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Pleural infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pneumonia  1  25/355 (7.04%)  32 35/354 (9.89%)  39
Rhinitis infective  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Salivary gland infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Sepsis  1  23/355 (6.48%)  27 16/354 (4.52%)  17
Sinusitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Skin infection  1  8/355 (2.25%)  9 8/354 (2.26%)  9
Small intestine infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Soft tissue infection  1  0/355 (0.00%)  0 4/354 (1.13%)  4
Splenic infection  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Tooth infection  1  1/355 (0.28%)  1 4/354 (1.13%)  5
Upper aerodigestive tract infection  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Urinary tract infection  1  8/355 (2.25%)  10 15/354 (4.24%)  19
Vulval infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Wound infection  1  4/355 (1.13%)  4 2/354 (0.56%)  2
Injury, poisoning and procedural complications     
Bruising  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Fracture  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Gastrointestinal anastomotic leak  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative complications  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Intraoperative gastrointestinal injury  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Intraoperative gastrointestinal injury - Appendix  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative reproductive tract injury - Ovary  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative reproductive tract injury - Testis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Kidney anastomotic leak  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Postoperative hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Thermal burn  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Vascular access complication  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Wound dehiscence  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Investigations     
Activated partial thromboplastin time prolonged  1  9/355 (2.54%)  15 9/354 (2.54%)  11
Alanine aminotransferase increased  1  35/355 (9.86%)  41 35/354 (9.89%)  41
Alkaline phosphatase increased  1  8/355 (2.25%)  8 20/354 (5.65%)  24
Amylase increased  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Aspartate aminotransferase increased  1  30/355 (8.45%)  33 29/354 (8.19%)  32
Blood bilirubin increased  1  25/355 (7.04%)  32 36/354 (10.17%)  42
CD4 lymphocytes decreased  1  1/355 (0.28%)  3 0/354 (0.00%)  0
Cardiac troponin T increased  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Coagulopathy  1  8/355 (2.25%)  14 7/354 (1.98%)  11
Creatinine increased  1  15/355 (4.23%)  16 16/354 (4.52%)  17
Electrocardiogram QTc interval prolonged  1  17/355 (4.79%)  22 19/354 (5.37%)  22
Fibrinogen decreased  1  2/355 (0.56%)  2 7/354 (1.98%)  7
Gamma-glutamyltransferase increased  1  19/355 (5.35%)  25 22/354 (6.21%)  32
INR increased  1  8/355 (2.25%)  10 5/354 (1.41%)  5
Laboratory test abnormal  1  18/355 (5.07%)  33 28/354 (7.91%)  47
Leukocyte count decreased  1  41/355 (11.55%)  66 47/354 (13.28%)  78
Lipase increased  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Lymphocyte count decreased  1  22/355 (6.20%)  30 36/354 (10.17%)  56
Neutrophil count decreased  1  145/355 (40.85%)  227 146/354 (41.24%)  224
Platelet count decreased  1  155/355 (43.66%)  239 146/354 (41.24%)  227
Serum cholesterol increased  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Weight gain  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Weight loss  1  1/355 (0.28%)  1 11/354 (3.11%)  13
Metabolism and nutrition disorders     
Acidosis  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Anorexia  1  21/355 (5.92%)  30 26/354 (7.34%)  29
Blood glucose increased  1  17/355 (4.79%)  23 22/354 (6.21%)  31
Blood uric acid increased  1  6/355 (1.69%)  10 4/354 (1.13%)  4
Dehydration  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Glucose intolerance  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Serum albumin decreased  1  19/355 (5.35%)  28 22/354 (6.21%)  26
Serum calcium decreased  1  20/355 (5.63%)  25 26/354 (7.34%)  30
Serum calcium increased  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Serum glucose decreased  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Serum magnesium decreased  1  15/355 (4.23%)  19 15/354 (4.24%)  22
Serum phosphate decreased  1  7/355 (1.97%)  9 12/354 (3.39%)  13
Serum potassium decreased  1  31/355 (8.73%)  37 47/354 (13.28%)  53
Serum potassium increased  1  8/355 (2.25%)  9 4/354 (1.13%)  4
Serum sodium decreased  1  20/355 (5.63%)  22 20/354 (5.65%)  22
Serum sodium increased  1  5/355 (1.41%)  5 5/354 (1.41%)  5
Serum triglycerides increased  1  3/355 (0.85%)  4 0/354 (0.00%)  0
Tumor lysis syndrome  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  8/355 (2.25%)  8 6/354 (1.69%)  6
Arthritis  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Back pain  1  15/355 (4.23%)  19 13/354 (3.67%)  13
Bone pain  1  7/355 (1.97%)  8 4/354 (1.13%)  5
Buttock pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Chest wall pain  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Joint effusion  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Muscle weakness  1  3/355 (0.85%)  3 2/354 (0.56%)  3
Musculoskeletal disorder  1  4/355 (1.13%)  4 4/354 (1.13%)  4
Myalgia  1  7/355 (1.97%)  7 4/354 (1.13%)  5
Neck pain  1  7/355 (1.97%)  8 4/354 (1.13%)  5
Pain in extremity  1  5/355 (1.41%)  6 6/354 (1.69%)  9
Trismus  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Nervous system disorders     
Ataxia  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Depressed level of consciousness  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Dizziness  1  19/355 (5.35%)  23 20/354 (5.65%)  25
Dysgeusia  1  4/355 (1.13%)  4 7/354 (1.98%)  9
Encephalopathy  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Extrapyramidal disorder  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Headache  1  41/355 (11.55%)  54 42/354 (11.86%)  63
Intracranial hemorrhage  1  3/355 (0.85%)  3 6/354 (1.69%)  6
Ischemia cerebrovascular  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Memory impairment  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Neuralgia  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Neurological disorder NOS  1  9/355 (2.54%)  11 4/354 (1.13%)  4
Nystagmus  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Peripheral motor neuropathy  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Peripheral sensory neuropathy  1  5/355 (1.41%)  5 6/354 (1.69%)  11
Seizure  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Speech disorder  1  4/355 (1.13%)  4 1/354 (0.28%)  1
Syncope  1  6/355 (1.69%)  6 4/354 (1.13%)  4
Syncope vasovagal  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Tremor  1  4/355 (1.13%)  4 3/354 (0.85%)  3
Psychiatric disorders     
Agitation  1  3/355 (0.85%)  5 3/354 (0.85%)  3
Anxiety  1  5/355 (1.41%)  5 9/354 (2.54%)  11
Confusion  1  4/355 (1.13%)  4 3/354 (0.85%)  3
Depression  1  2/355 (0.56%)  2 12/354 (3.39%)  12
Euphoria  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Insomnia  1  11/355 (3.10%)  14 7/354 (1.98%)  11
Personality change  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Psychosis  1  4/355 (1.13%)  4 2/354 (0.56%)  2
Renal and urinary disorders     
Bladder hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bladder pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Cystitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Glomerular filtration rate decreased  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Hemorrhage urinary tract  1  2/355 (0.56%)  2 6/354 (1.69%)  6
Proteinuria  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Renal failure  1  13/355 (3.66%)  13 9/354 (2.54%)  9
Renal hemorrhage  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Ureteric obstruction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Urethral pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Urinary frequency  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Urinary incontinence  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Urinary retention  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Urine discoloration  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Urogenital disorder  1  15/355 (4.23%)  21 11/354 (3.11%)  15
Reproductive system and breast disorders     
Breast pain  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Penile pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Perineal pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Reproductive tract disorder  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Uterine hemorrhage  1  4/355 (1.13%)  5 3/354 (0.85%)  4
Vaginal hemorrhage  1  5/355 (1.41%)  5 9/354 (2.54%)  9
Vaginal mucositis  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Vaginal pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  9/355 (2.54%)  9 5/354 (1.41%)  5
Allergic rhinitis  1  1/355 (0.28%)  1 3/354 (0.85%)  4
Aspiration  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Atelectasis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bronchopulmonary hemorrhage  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Bronchospasm  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Cough  1  17/355 (4.79%)  21 19/354 (5.37%)  20
Dyspnea  1  20/355 (5.63%)  22 24/354 (6.78%)  24
Epistaxis  1  24/355 (6.76%)  26 22/354 (6.21%)  24
Hiccups  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Hypoxia  1  8/355 (2.25%)  8 12/354 (3.39%)  12
Laryngeal edema  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Laryngeal mucositis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Laryngeal pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Laryngoscopy abnormal  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Nasal congestion  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pharyngeal examination abnormal  1  3/355 (0.85%)  3 2/354 (0.56%)  2
Pharyngeal mucositis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Pharyngolaryngeal pain  1  6/355 (1.69%)  6 11/354 (3.11%)  12
Pleural effusion  1  8/355 (2.25%)  8 8/354 (2.26%)  8
Pleuritic pain  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Pneumonitis  1  27/355 (7.61%)  28 17/354 (4.80%)  19
Pneumothorax  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Pulmonary hemorrhage  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Pulmonary hypertension  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Respiratory disorder  1  12/355 (3.38%)  12 9/354 (2.54%)  9
Respiratory tract hemorrhage  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Retinoic acid syndrome  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Tracheal stenosis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Voice alteration  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  6/355 (1.69%)  8 4/354 (1.13%)  4
Decubitus ulcer  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Dry skin  1  7/355 (1.97%)  8 7/354 (1.98%)  7
Erythema multiforme  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Hand-and-foot syndrome  1  2/355 (0.56%)  4 5/354 (1.41%)  5
Nail disorder  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pain of skin  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Petechiae  1  35/355 (9.86%)  45 34/354 (9.60%)  52
Pruritus  1  11/355 (3.10%)  13 12/354 (3.39%)  13
Rash acneiform  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Rash desquamating  1  59/355 (16.62%)  70 66/354 (18.64%)  71
Skin disorder  1  23/355 (6.48%)  28 23/354 (6.50%)  30
Skin hyperpigmentation  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Skin ulceration  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Sweating  1  14/355 (3.94%)  19 14/354 (3.95%)  15
Urticaria  1  3/355 (0.85%)  3 3/354 (0.85%)  4
Vascular disorders     
Flushing  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Hematoma  1  14/355 (3.94%)  17 13/354 (3.67%)  17
Hemorrhage  1  14/355 (3.94%)  19 12/354 (3.39%)  13
Hot flashes  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Hypertension  1  13/355 (3.66%)  13 11/354 (3.11%)  11
Hypotension  1  25/355 (7.04%)  26 19/354 (5.37%)  22
Lymphangitic streak  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Lymphedema  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Phlebitis  1  6/355 (1.69%)  7 7/354 (1.98%)  7
Thrombosis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Vascular disorder  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Vasculitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Induction and Consolidation Chemotherapy Plus Midostaurin Induction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   321/355 (90.42%)      324/354 (91.53%)    
Blood and lymphatic system disorders     
Blood disorder  1  5/355 (1.41%)  11 4/354 (1.13%)  6
Disseminated intravascular coagulation  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Febrile neutropenia  1  246/355 (69.30%)  422 238/354 (67.23%)  394
Hemoglobin decreased  1  312/355 (87.89%)  1059 311/354 (87.85%)  940
Lymph node pain  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Lymphatic disorder  1  10/355 (2.82%)  13 9/354 (2.54%)  11
Cardiac disorders     
Arrhythmia  1  1/355 (0.28%)  1 4/354 (1.13%)  4
Atrial fibrillation  1  3/355 (0.85%)  3 0/354 (0.00%)  0
Atrial flutter  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Atrial tachycardia  1  1/355 (0.28%)  3 1/354 (0.28%)  1
Cardiac disorder  1  8/355 (2.25%)  12 13/354 (3.67%)  17
Cardiac pain  1  4/355 (1.13%)  6 1/354 (0.28%)  1
Cardiac valve disease  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Conduction disorder  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Left ventricular failure  1  6/355 (1.69%)  6 5/354 (1.41%)  9
Myocardial ischemia  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Palpitations  1  3/355 (0.85%)  3 5/354 (1.41%)  13
Pericardial effusion  1  7/355 (1.97%)  8 1/354 (0.28%)  1
Pericarditis  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Premature ventricular contractions  1  1/355 (0.28%)  3 0/354 (0.00%)  0
Sinus bradycardia  1  10/355 (2.82%)  10 5/354 (1.41%)  15
Sinus tachycardia  1  11/355 (3.10%)  13 23/354 (6.50%)  29
Supraventricular extrasystoles  1  1/355 (0.28%)  1 2/354 (0.56%)  7
Supraventricular tachycardia  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Ventricular arrhythmia  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Ventricular bigeminy  1  1/355 (0.28%)  2 0/354 (0.00%)  0
Ventricular fibrillation  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Ventricular tachycardia  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Ear and labyrinth disorders     
Ear disorder  1  5/355 (1.41%)  5 3/354 (0.85%)  3
Ear pain  1  5/355 (1.41%)  6 6/354 (1.69%)  6
External ear inflammation  1  0/355 (0.00%)  0 2/354 (0.56%)  2
External ear pain  1  3/355 (0.85%)  3 2/354 (0.56%)  2
Hearing impaired  1  2/355 (0.56%)  4 2/354 (0.56%)  2
Middle ear inflammation  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Tinnitus  1  3/355 (0.85%)  3 2/354 (0.56%)  2
Endocrine disorders     
Endocrine disorder  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Hyperthyroidism  1  2/355 (0.56%)  7 1/354 (0.28%)  3
Hypothyroidism  1  2/355 (0.56%)  2 2/354 (0.56%)  5
Eye disorders     
Cataract  1  1/355 (0.28%)  9 0/354 (0.00%)  0
Conjunctivitis  1  7/355 (1.97%)  7 4/354 (1.13%)  5
Dry eye syndrome  1  5/355 (1.41%)  7 10/354 (2.82%)  12
Eye disorder  1  21/355 (5.92%)  28 16/354 (4.52%)  19
Eye pain  1  5/355 (1.41%)  5 5/354 (1.41%)  5
Eyelid function disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Flashing vision  1  1/355 (0.28%)  1 4/354 (1.13%)  5
Keratitis  1  14/355 (3.94%)  17 9/354 (2.54%)  14
Optic nerve disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Photophobia  1  2/355 (0.56%)  3 4/354 (1.13%)  4
Vision blurred  1  5/355 (1.41%)  8 4/354 (1.13%)  7
Vitreous hemorrhage  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Watering eyes  1  4/355 (1.13%)  7 2/354 (0.56%)  2
Gastrointestinal disorders     
Abdominal distension  1  6/355 (1.69%)  15 10/354 (2.82%)  11
Abdominal pain  1  57/355 (16.06%)  78 67/354 (18.93%)  84
Anal exam abnormal  1  0/355 (0.00%)  0 3/354 (0.85%)  3
Anal fistula  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Anal hemorrhage  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Anal mucositis  1  2/355 (0.56%)  2 2/354 (0.56%)  3
Anal pain  1  12/355 (3.38%)  15 6/354 (1.69%)  8
Anal ulcer  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Ascites  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Colitis  1  7/355 (1.97%)  9 12/354 (3.39%)  18
Colonic hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Colonic perforation  1  0/355 (0.00%)  0 1/354 (0.28%)  2
Constipation  1  50/355 (14.08%)  86 60/354 (16.95%)  83
Dental prosthesis user  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Diarrhea  1  228/355 (64.23%)  432 219/354 (61.86%)  310
Dry mouth  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Dyspepsia  1  22/355 (6.20%)  36 16/354 (4.52%)  17
Dysphagia  1  6/355 (1.69%)  6 10/354 (2.82%)  10
Ear, nose and throat examination abnormal  1  112/355 (31.55%)  178 112/354 (31.64%)  169
Endoscopy large bowel abnormal  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Enteritis  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Esophageal mucositis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Esophageal pain  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Esophageal perforation  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Esophageal ulcer  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Esophagitis  1  3/355 (0.85%)  3 4/354 (1.13%)  4
Flatulence  1  10/355 (2.82%)  20 7/354 (1.98%)  8
Gastric hemorrhage  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Gastric mucositis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Gastric ulcer  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Gastritis  1  3/355 (0.85%)  3 4/354 (1.13%)  4
Gastrointestinal disorder  1  28/355 (7.89%)  35 26/354 (7.34%)  29
Gastrointestinal pain  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Gastroscopy abnormal  1  0/355 (0.00%)  0 3/354 (0.85%)  3
Gingival pain  1  3/355 (0.85%)  3 4/354 (1.13%)  4
Hemorrhoidal hemorrhage  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Hemorrhoids  1  28/355 (7.89%)  36 21/354 (5.93%)  25
Ileal obstruction  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Ileus  1  2/355 (0.56%)  3 3/354 (0.85%)  3
Large intestinal mucositis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Mucositis oral  1  49/355 (13.80%)  59 31/354 (8.76%)  36
Nausea  1  258/355 (72.68%)  807 226/354 (63.84%)  449
Oesophagoscopy abnormal  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Oral hemorrhage  1  12/355 (3.38%)  13 18/354 (5.08%)  27
Oral pain  1  8/355 (2.25%)  10 11/354 (3.11%)  11
Periodontal disease  1  4/355 (1.13%)  6 7/354 (1.98%)  7
Peritoneal pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Proctitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Proctoscopy abnormal  1  3/355 (0.85%)  3 0/354 (0.00%)  0
Rectal hemorrhage  1  7/355 (1.97%)  8 5/354 (1.41%)  7
Rectal obstruction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Rectal pain  1  5/355 (1.41%)  6 2/354 (0.56%)  2
Salivary gland disorder  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Small intestinal mucositis  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Stomach pain  1  34/355 (9.58%)  43 27/354 (7.63%)  32
Tooth development disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Tooth disorder  1  6/355 (1.69%)  6 2/354 (0.56%)  2
Toothache  1  9/355 (2.54%)  11 10/354 (2.82%)  10
Typhlitis  1  3/355 (0.85%)  3 4/354 (1.13%)  4
Upper gastrointestinal hemorrhage  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Vomiting  1  188/355 (52.96%)  376 168/354 (47.46%)  259
General disorders     
Chest pain  1  15/355 (4.23%)  17 20/354 (5.65%)  28
Chills  1  22/355 (6.20%)  26 17/354 (4.80%)  21
Disease progression  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Edema limbs  1  33/355 (9.30%)  43 39/354 (11.02%)  56
Facial pain  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Fatigue  1  221/355 (62.25%)  522 220/354 (62.15%)  474
Fever  1  72/355 (20.28%)  110 69/354 (19.49%)  107
Flu-like symptoms  1  5/355 (1.41%)  5 2/354 (0.56%)  2
Gait abnormal  1  1/355 (0.28%)  1 0/354 (0.00%)  0
General symptom  1  15/355 (4.23%)  18 17/354 (4.80%)  25
Hypothermia  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Ill-defined disorder  1  3/355 (0.85%)  4 4/354 (1.13%)  4
Injection site reaction  1  20/355 (5.63%)  25 23/354 (6.50%)  34
Localized edema  1  16/355 (4.51%)  16 14/354 (3.95%)  19
Pain  1  40/355 (11.27%)  55 33/354 (9.32%)  44
Visceral edema  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Hepatobiliary disorders     
Cholecystitis  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Gallbladder pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Hepatic failure  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Hepatobiliary disease  1  4/355 (1.13%)  16 4/354 (1.13%)  5
Immune system disorders     
Cytokine release syndrome  1  1/355 (0.28%)  2 0/354 (0.00%)  0
Hypersensitivity  1  36/355 (10.14%)  41 30/354 (8.47%)  41
Immune system disorder  1  12/355 (3.38%)  14 9/354 (2.54%)  14
Infections and infestations     
Abdominal infection  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Anal infection  1  8/355 (2.25%)  9 8/354 (2.26%)  12
Anorectal infection  1  2/355 (0.56%)  3 1/354 (0.28%)  1
Appendicitis  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Bladder infection  1  8/355 (2.25%)  13 10/354 (2.82%)  11
Bone infection  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bronchitis  1  7/355 (1.97%)  9 6/354 (1.69%)  6
Catheter related infection  1  55/355 (15.49%)  74 43/354 (12.15%)  54
Cecal infection  1  1/355 (0.28%)  1 1/354 (0.28%)  2
Colitis, infectious (e.g., Clostridium difficile)  1  4/355 (1.13%)  4 4/354 (1.13%)  4
Conjunctivitis infective  1  8/355 (2.25%)  10 5/354 (1.41%)  7
Device related infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Eye infection  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Gastric infection  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Gingival infection  1  5/355 (1.41%)  6 3/354 (0.85%)  3
Hepatic infection  1  3/355 (0.85%)  3 5/354 (1.41%)  14
Infection  1  57/355 (16.06%)  100 60/354 (16.95%)  99
Infectious colitis  1  5/355 (1.41%)  7 5/354 (1.41%)  5
Kidney infection  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Lip infection  1  17/355 (4.79%)  22 21/354 (5.93%)  29
Lymph gland infection  1  1/355 (0.28%)  1 3/354 (0.85%)  4
Mediastinal infection  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Mucosal infection  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Nail infection  1  3/355 (0.85%)  4 2/354 (0.56%)  2
Opportunistic infection  1  4/355 (1.13%)  5 9/354 (2.54%)  14
Otitis media  1  2/355 (0.56%)  3 0/354 (0.00%)  0
Paranasal sinus infection  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Penile infection  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Pharyngitis  1  5/355 (1.41%)  5 7/354 (1.98%)  7
Phlebitis infective  1  3/355 (0.85%)  5 2/354 (0.56%)  2
Pneumonia  1  36/355 (10.14%)  53 36/354 (10.17%)  45
Rhinitis infective  1  6/355 (1.69%)  12 6/354 (1.69%)  7
Scrotal infection  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Sepsis  1  26/355 (7.32%)  29 20/354 (5.65%)  23
Sinusitis  1  7/355 (1.97%)  7 5/354 (1.41%)  6
Skin infection  1  22/355 (6.20%)  24 15/354 (4.24%)  19
Soft tissue infection  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Splenic infection  1  1/355 (0.28%)  1 2/354 (0.56%)  9
Tooth infection  1  4/355 (1.13%)  4 4/354 (1.13%)  5
Tracheitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Upper aerodigestive tract infection  1  0/355 (0.00%)  0 4/354 (1.13%)  4
Upper respiratory infection  1  11/355 (3.10%)  17 8/354 (2.26%)  14
Ureteritis  1  4/355 (1.13%)  6 4/354 (1.13%)  6
Urinary tract infection  1  15/355 (4.23%)  17 15/354 (4.24%)  19
Vaginal infection  1  5/355 (1.41%)  6 8/354 (2.26%)  12
Viral hepatitis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Vulval infection  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Vulvitis  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Wound infection  1  3/355 (0.85%)  3 3/354 (0.85%)  3
Injury, poisoning and procedural complications     
Bruising  1  3/355 (0.85%)  3 1/354 (0.28%)  1
Device complication  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Fracture  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Injury to inferior vena cava  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Injury to jugular vein  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative complications  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Intraoperative gastrointestinal injury  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative gastrointestinal injury - Teeth  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Intraoperative head and neck injury - Neck NOS  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Intraoperative ocular injury - Lens  1  1/355 (0.28%)  2 0/354 (0.00%)  0
Postoperative hemorrhage  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Radiation recall reaction (dermatologic)  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Thermal burn  1  0/355 (0.00%)  0 3/354 (0.85%)  3
Tracheostomy site bleeding  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Vaginal anastomotic leak  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Vascular access complication  1  9/355 (2.54%)  15 6/354 (1.69%)  6
Venous injury - Extremity-lower  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Wound dehiscence  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Investigations     
Activated partial thromboplastin time prolonged  1  26/355 (7.32%)  36 22/354 (6.21%)  27
Alanine aminotransferase increased  1  88/355 (24.79%)  312 83/354 (23.45%)  184
Alkaline phosphatase increased  1  30/355 (8.45%)  60 29/354 (8.19%)  55
Amylase increased  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Aspartate aminotransferase increased  1  60/355 (16.90%)  201 56/354 (15.82%)  102
Blood bilirubin increased  1  49/355 (13.80%)  86 60/354 (16.95%)  104
Cardiac troponin T increased  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Coagulopathy  1  7/355 (1.97%)  8 10/354 (2.82%)  14
Creatinine increased  1  13/355 (3.66%)  18 15/354 (4.24%)  25
Electrocardiogram QTc interval prolonged  1  45/355 (12.68%)  81 36/354 (10.17%)  48
Fibrinogen decreased  1  12/355 (3.38%)  14 8/354 (2.26%)  10
Forced expiratory volume decreased  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Gamma-glutamyltransferase increased  1  25/355 (7.04%)  55 34/354 (9.60%)  57
INR increased  1  9/355 (2.54%)  11 12/354 (3.39%)  12
Laboratory test abnormal  1  31/355 (8.73%)  53 41/354 (11.58%)  81
Leukocyte count decreased  1  79/355 (22.25%)  240 92/354 (25.99%)  204
Lymphocyte count decreased  1  69/355 (19.44%)  195 71/354 (20.06%)  158
Neutrophil count decreased  1  308/355 (86.76%)  952 308/354 (87.01%)  879
Platelet count decreased  1  311/355 (87.61%)  1131 313/354 (88.42%)  1020
Serum cholesterol increased  1  0/355 (0.00%)  0 5/354 (1.41%)  10
Weight gain  1  15/355 (4.23%)  26 6/354 (1.69%)  11
Weight loss  1  9/355 (2.54%)  12 10/354 (2.82%)  12
Metabolism and nutrition disorders     
Alkalosis  1  0/355 (0.00%)  0 3/354 (0.85%)  3
Anorexia  1  30/355 (8.45%)  40 40/354 (11.30%)  50
Blood glucose increased  1  72/355 (20.28%)  202 59/354 (16.67%)  134
Blood uric acid increased  1  21/355 (5.92%)  42 15/354 (4.24%)  23
Dehydration  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Glucose intolerance  1  0/355 (0.00%)  0 2/354 (0.56%)  5
Iron overload  1  0/355 (0.00%)  0 2/354 (0.56%)  4
Serum albumin decreased  1  56/355 (15.77%)  101 56/354 (15.82%)  80
Serum calcium decreased  1  58/355 (16.34%)  88 56/354 (15.82%)  79
Serum calcium increased  1  6/355 (1.69%)  11 1/354 (0.28%)  2
Serum glucose decreased  1  6/355 (1.69%)  8 9/354 (2.54%)  10
Serum magnesium decreased  1  30/355 (8.45%)  48 32/354 (9.04%)  65
Serum magnesium increased  1  7/355 (1.97%)  8 3/354 (0.85%)  3
Serum phosphate decreased  1  27/355 (7.61%)  31 27/354 (7.63%)  40
Serum potassium decreased  1  79/355 (22.25%)  117 74/354 (20.90%)  112
Serum potassium increased  1  5/355 (1.41%)  5 5/354 (1.41%)  6
Serum sodium decreased  1  48/355 (13.52%)  63 51/354 (14.41%)  64
Serum sodium increased  1  8/355 (2.25%)  8 8/354 (2.26%)  9
Serum triglycerides increased  1  1/355 (0.28%)  1 4/354 (1.13%)  5
Tumor lysis syndrome  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Musculoskeletal and connective tissue disorders     
Arthralgia  1  30/355 (8.45%)  67 16/354 (4.52%)  25
Arthritis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Back pain  1  46/355 (12.96%)  74 34/354 (9.60%)  53
Bone pain  1  19/355 (5.35%)  32 21/354 (5.93%)  37
Buttock pain  1  3/355 (0.85%)  3 0/354 (0.00%)  0
Chest wall pain  1  6/355 (1.69%)  9 3/354 (0.85%)  4
Joint disorder  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Joint effusion  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Joint range of motion decreased lumbar spine  1  1/355 (0.28%)  2 0/354 (0.00%)  0
Muscle weakness  1  6/355 (1.69%)  6 4/354 (1.13%)  4
Muscle weakness lower limb  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Musculoskeletal disorder  1  13/355 (3.66%)  19 6/354 (1.69%)  8
Myalgia  1  13/355 (3.66%)  24 16/354 (4.52%)  19
Myositis  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Neck pain  1  16/355 (4.51%)  18 9/354 (2.54%)  9
Osteoporosis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Pain in extremity  1  30/355 (8.45%)  39 17/354 (4.80%)  23
Upper extremity dysfunction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Myelodysplasia  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Treatment related secondary malignancy  1  1/355 (0.28%)  1 1/354 (0.28%)  2
Tumor pain  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Nervous system disorders     
Ataxia  1  2/355 (0.56%)  2 10/354 (2.82%)  11
Cognitive disturbance  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Depressed level of consciousness  1  2/355 (0.56%)  2 3/354 (0.85%)  3
Dizziness  1  44/355 (12.39%)  64 43/354 (12.15%)  55
Dysgeusia  1  5/355 (1.41%)  5 11/354 (3.11%)  14
Encephalopathy  1  0/355 (0.00%)  0 1/354 (0.28%)  5
Extrapyramidal disorder  1  0/355 (0.00%)  0 2/354 (0.56%)  5
Headache  1  105/355 (29.58%)  218 85/354 (24.01%)  143
Intracranial hemorrhage  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Memory impairment  1  2/355 (0.56%)  4 1/354 (0.28%)  2
Neuralgia  1  2/355 (0.56%)  2 3/354 (0.85%)  6
Neurological disorder NOS  1  17/355 (4.79%)  22 7/354 (1.98%)  7
Olfactory nerve disorder  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Peripheral motor neuropathy  1  2/355 (0.56%)  12 1/354 (0.28%)  1
Peripheral sensory neuropathy  1  6/355 (1.69%)  21 11/354 (3.11%)  26
Pyramidal tract syndrome  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Seizure  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Speech disorder  1  1/355 (0.28%)  16 1/354 (0.28%)  1
Syncope  1  8/355 (2.25%)  9 6/354 (1.69%)  6
Syncope vasovagal  1  2/355 (0.56%)  3 7/354 (1.98%)  9
Tremor  1  5/355 (1.41%)  8 4/354 (1.13%)  4
Psychiatric disorders     
Agitation  1  4/355 (1.13%)  4 3/354 (0.85%)  3
Anxiety  1  16/355 (4.51%)  21 18/354 (5.08%)  32
Confusion  1  4/355 (1.13%)  5 4/354 (1.13%)  4
Depression  1  14/355 (3.94%)  26 24/354 (6.78%)  50
Euphoria  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Insomnia  1  30/355 (8.45%)  47 20/354 (5.65%)  35
Personality change  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Psychosis  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Renal and urinary disorders     
Bladder hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bladder pain  1  3/355 (0.85%)  5 1/354 (0.28%)  1
Bladder spasm  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Cystitis  1  5/355 (1.41%)  6 7/354 (1.98%)  8
Hemoglobin urine positive  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Hemorrhage urinary tract  1  2/355 (0.56%)  2 4/354 (1.13%)  4
Kidney pain  1  1/355 (0.28%)  2 0/354 (0.00%)  0
Proteinuria  1  1/355 (0.28%)  3 1/354 (0.28%)  1
Renal failure  1  3/355 (0.85%)  3 1/354 (0.28%)  1
Urethral obstruction  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Urethral pain  1  0/355 (0.00%)  0 2/354 (0.56%)  2
Urinary frequency  1  1/355 (0.28%)  1 4/354 (1.13%)  9
Urinary incontinence  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Urinary retention  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Urine discoloration  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Urogenital disorder  1  11/355 (3.10%)  12 10/354 (2.82%)  11
Reproductive system and breast disorders     
Breast pain  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Gynecomastia  1  1/355 (0.28%)  1 1/354 (0.28%)  3
Pelvic pain  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Perineal pain  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Reproductive tract disorder  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Uterine hemorrhage  1  8/355 (2.25%)  12 6/354 (1.69%)  7
Uterine pain  1  1/355 (0.28%)  1 3/354 (0.85%)  3
Vaginal discharge  1  1/355 (0.28%)  1 1/354 (0.28%)  2
Vaginal hemorrhage  1  16/355 (4.51%)  17 17/354 (4.80%)  24
Vaginal inflammation  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Vaginal mucositis  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Vaginal pain  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  1/355 (0.28%)  1 1/354 (0.28%)  1
Allergic rhinitis  1  3/355 (0.85%)  3 8/354 (2.26%)  14
Atelectasis  1  1/355 (0.28%)  1 2/354 (0.56%)  2
Bronchopulmonary hemorrhage  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Bronchospasm  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Cough  1  38/355 (10.70%)  57 41/354 (11.58%)  51
Dyspnea  1  28/355 (7.89%)  33 29/354 (8.19%)  30
Epistaxis  1  55/355 (15.49%)  63 46/354 (12.99%)  62
Hypoxia  1  9/355 (2.54%)  9 11/354 (3.11%)  11
Laryngeal edema  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Laryngeal mucositis  1  1/355 (0.28%)  1 2/354 (0.56%)  3
Laryngeal pain  1  2/355 (0.56%)  2 1/354 (0.28%)  1
Laryngoscopy abnormal  1  2/355 (0.56%)  2 1/354 (0.28%)  2
Nasal congestion  1  4/355 (1.13%)  4 4/354 (1.13%)  6
Pharyngeal examination abnormal  1  2/355 (0.56%)  2 6/354 (1.69%)  6
Pharyngeal mucositis  1  4/355 (1.13%)  4 1/354 (0.28%)  1
Pharyngeal stenosis  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pharyngolaryngeal pain  1  28/355 (7.89%)  35 25/354 (7.06%)  30
Pleural effusion  1  9/355 (2.54%)  9 6/354 (1.69%)  6
Pneumonitis  1  23/355 (6.48%)  33 33/354 (9.32%)  40
Pneumothorax  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Pulmonary fibrosis  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Respiratory disorder  1  17/355 (4.79%)  23 21/354 (5.93%)  31
Voice alteration  1  3/355 (0.85%)  4 1/354 (0.28%)  1
Skin and subcutaneous tissue disorders     
Alopecia  1  8/355 (2.25%)  10 6/354 (1.69%)  9
Decubitus ulcer  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Dry skin  1  11/355 (3.10%)  13 9/354 (2.54%)  12
Erythema multiforme  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Hand-and-foot syndrome  1  8/355 (2.25%)  9 9/354 (2.54%)  11
Nail disorder  1  1/355 (0.28%)  3 0/354 (0.00%)  0
Pain of skin  1  3/355 (0.85%)  3 2/354 (0.56%)  2
Petechiae  1  67/355 (18.87%)  89 51/354 (14.41%)  68
Photosensitivity  1  3/355 (0.85%)  5 0/354 (0.00%)  0
Pruritus  1  25/355 (7.04%)  31 31/354 (8.76%)  41
Rash acneiform  1  2/355 (0.56%)  2 2/354 (0.56%)  2
Rash desquamating  1  201/355 (56.62%)  358 200/354 (56.50%)  317
Skin disorder  1  44/355 (12.39%)  67 42/354 (11.86%)  58
Skin hyperpigmentation  1  1/355 (0.28%)  3 3/354 (0.85%)  4
Skin induration  1  0/355 (0.00%)  0 1/354 (0.28%)  2
Skin striae  1  1/355 (0.28%)  1 0/354 (0.00%)  0
Skin ulceration  1  5/355 (1.41%)  6 6/354 (1.69%)  8
Sweating  1  30/355 (8.45%)  50 19/354 (5.37%)  32
Urticaria  1  6/355 (1.69%)  7 5/354 (1.41%)  5
Vascular disorders     
Flushing  1  0/355 (0.00%)  0 2/354 (0.56%)  3
Hematoma  1  32/355 (9.01%)  40 34/354 (9.60%)  39
Hemorrhage  1  15/355 (4.23%)  22 31/354 (8.76%)  33
Hot flashes  1  2/355 (0.56%)  4 4/354 (1.13%)  4
Hypertension  1  15/355 (4.23%)  21 13/354 (3.67%)  25
Hypotension  1  32/355 (9.01%)  37 32/354 (9.04%)  36
Lymphedema  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Lymphocele  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Phlebitis  1  13/355 (3.66%)  19 15/354 (4.24%)  17
Thrombosis  1  6/355 (1.69%)  6 3/354 (0.85%)  3
Vascular disorder  1  0/355 (0.00%)  0 4/354 (1.13%)  4
Vasculitis  1  2/355 (0.56%)  2 0/354 (0.00%)  0
Visceral arterial ischemia  1  0/355 (0.00%)  0 1/354 (0.28%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Richard Stone, MD
Organization: Dana Farber Cancer Institute
Publications of Results:
Stone RM, Dohner H, Ehninger G, et al.: CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS199, 2011.
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00651261     History of Changes
Other Study ID Numbers: CALGB-10603
CALGB-10603
EUDRACT-2006-006852-37
CDR0000590404 ( Registry Identifier: Phyisician Data Query )
First Submitted: April 1, 2008
First Posted: April 2, 2008
Results First Submitted: December 12, 2016
Results First Posted: February 6, 2017
Last Update Posted: July 9, 2019