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A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02421939
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Results First Posted : October 17, 2019
Last Update Posted : March 16, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Acute Myeloid (AML)
Interventions Drug: gilteritinib
Drug: LoDAC (Low Dose Cytarabine)
Drug: Azacitidine
Drug: MEC (Mitoxantrone, Etoposide, Cytarabine)
Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin)
Enrollment 371
Recruitment Details Participants were recruited from approximately 140 centers in North America, Europe, Asia and the rest of the world and randomized in a 2:1 ratio to receive gilteritinib or salvage chemotherapy. Participants had FMS-like tyrosine kinase 3 (FLT3) mutations and relapsed or refractory acute myeloid leukemia (AML) after first-line therapy.
Pre-assignment Details Participants entered the screening period up to 14 days prior to the start of treatment. Prior to randomization, the investigator preselected a salvage chemotherapy for each participant. The randomization was stratified by response to first-line AML therapy and preselected salvage chemotherapy. Treatment was given over continuous 28-day cycles.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria. Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Period Title: Overall Study
Started 247 124
Treated 246 109
Completed [1] 38 0
Not Completed 209 124
Reason Not Completed
Progressive disease             70             16
Lack of Efficacy             21             31
Death             36             10
Disease relapse             33             2
Adverse Event             28             5
Withdrawal by Subject             5             24
Physician Decision             11             11
Completed 1 or 2 chemo cycles with CRs             0             19
Miscellaneous             4             5
Protocol deviation             1             1
[1]
Participants still on treatment. Last assessment of remission status at the end of treatment visit.
Arm/Group Title Gilteritinib Salvage Chemotherapy Total
Hide Arm/Group Description Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria. Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15. Total of all reporting groups
Overall Number of Baseline Participants 247 124 371
Hide Baseline Analysis Population Description
The analysis population was the Intention to Treatment (ITT), which consisted of all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 247 participants 124 participants 371 participants
59  (14.6) 57.6  (14.8) 58.5  (14.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
Female
131
  53.0%
70
  56.5%
201
  54.2%
Male
116
  47.0%
54
  43.5%
170
  45.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
WHITE
145
  58.7%
75
  60.5%
220
  59.3%
ASIAN
69
  27.9%
33
  26.6%
102
  27.5%
BLACK OR AFRICAN AMERICAN
14
   5.7%
7
   5.6%
21
   5.7%
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
1
   0.4%
0
   0.0%
1
   0.3%
AMERICAN INDIAN OR ALASKA NATIVE
0
   0.0%
0
   0.0%
0
   0.0%
UNKNOWN
4
   1.6%
4
   3.2%
8
   2.2%
OTHER
5
   2.0%
1
   0.8%
6
   1.6%
MISSING
9
   3.6%
4
   3.2%
13
   3.5%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
NOT HISPANIC OR LATINO
221
  89.5%
116
  93.5%
337
  90.8%
HISPANIC OR LATINO
12
   4.9%
2
   1.6%
14
   3.8%
UNKNOWN
3
   1.2%
2
   1.6%
5
   1.3%
MISSING
11
   4.5%
4
   3.2%
15
   4.0%
Cytogenic Risk Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
INTERMEDIATE
182
  73.7%
89
  71.8%
271
  73.0%
UNFAVORABLE
26
  10.5%
11
   8.9%
37
  10.0%
FAVORABLE
4
   1.6%
1
   0.8%
5
   1.3%
OTHER
35
  14.2%
23
  18.5%
58
  15.6%
[1]
Measure Description: The category of “Other” includes those with cytogenetic risk status that cannot be categorized as favorable, intermediate or unfavorable.
Baseline Eastern Cooperative Oncology Group (ECOG)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
0-1
206
  83.4%
105
  84.7%
311
  83.8%
>=2
41
  16.6%
19
  15.3%
60
  16.2%
[1]
Measure Description: ECOG performance status is a scale used to assess impact on daily activities. It is based on the investigator assessment. Scores range from 0 to 5, with 0-signifying fully active participant; 1-restricted in physically strenuous activity; 2-ambulatory and capable of all self-care, unable to work; 3-capable of only limited self-care, confined to bed more than 50% of waking hours; 4-completely disabled and 5-dead. Negative numerical score indicates an improvement and positive numerical score indicates a decline in participant’s daily activities, indicating disease progression.
FLT3 Mutation Status by Central Testing by FLT3 CDx  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
FLT3-ITD Alone
215
  87.0%
113
  91.1%
328
  88.4%
FLT3-TKD Alone
21
   8.5%
10
   8.1%
31
   8.4%
FLT3-ITD and FLT3-TKD
7
   2.8%
0
   0.0%
7
   1.9%
Others (Unknown/Missing/Negative)
4
   1.6%
1
   0.8%
5
   1.3%
Prior Use of FLT3 Inhibitor   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
No
215
  87.0%
110
  88.7%
325
  87.6%
Yes
32
  13.0%
14
  11.3%
46
  12.4%
[1]
Measure Description: Prior use of FLT3 inhibitor is defined as 'Yes' if participants received prior AML therapy of midostaurin, sorafenib or quizartinib; otherwise, prior use of FLT3 inhibitor is assigned as No.
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 124 participants 371 participants
NORTH AMERICA
114
  46.2%
52
  41.9%
166
  44.7%
EUROPE
68
  27.5%
43
  34.7%
111
  29.9%
ASIA
65
  26.3%
29
  23.4%
94
  25.3%
Baseline Body Surface Area (BSA)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 199 participants 122 participants 321 participants
1.815  (0.281) 1.777  (0.257) 1.8  (0.272)
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
Baseline Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 234 participants 123 participants 357 participants
167.25  (10.31) 166.39  (10.63) 166.95  (10.41)
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
Baseline Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 243 participants 124 participants 367 participants
72.79  (20.47) 69.91  (19.73) 71.82  (20.25)
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
Response to First Line Therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Primary refractory without HSCT Number Analyzed 247 participants 124 participants 371 participants
98
  39.7%
48
  38.7%
146
  39.4%
Relapse within 6 months after CRc and no HSCT Number Analyzed 247 participants 124 participants 371 participants
67
  27.1%
34
  27.4%
101
  27.2%
Relapse after 6 months after CRc and no HSCT Number Analyzed 247 participants 124 participants 371 participants
34
  13.8%
17
  13.7%
51
  13.7%
Relapse within 6 months after allogeneic HSCT Number Analyzed 247 participants 124 participants 371 participants
31
  12.6%
17
  13.7%
48
  12.9%
Relapse after 6 months after allogeneic HSCT Number Analyzed 247 participants 124 participants 371 participants
17
   6.9%
8
   6.5%
25
   6.7%
[1]
Measure Description: Baseline stratification factors.
Preselected Salvage Chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
High intensity chemotherapy Number Analyzed 247 participants 124 participants 371 participants
149
  60.3%
75
  60.5%
224
  60.4%
Low intensity chemotherapy Number Analyzed 247 participants 124 participants 371 participants
98
  39.7%
49
  39.5%
147
  39.6%
[1]
Measure Description: Baseline stratification factors.
Response to First Line Therapy-Preselected Salvage Chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Primary refractory w/o HSCT, high intensity (IT) Number Analyzed 247 participants 124 participants 371 participants
57
  23.1%
28
  22.6%
85
  22.9%
Primary refractory w/o HSCT, low IT Number Analyzed 247 participants 124 participants 371 participants
41
  16.6%
20
  16.1%
61
  16.4%
Relapse w/I 6 mths after CRc and no HSCT, high IT Number Analyzed 247 participants 124 participants 371 participants
40
  16.2%
21
  16.9%
61
  16.4%
Relapse w/I 6 mths after CRc and no HSCT low IT Number Analyzed 247 participants 124 participants 371 participants
27
  10.9%
13
  10.5%
40
  10.8%
Relapse after 6 mths after CRc and no HSCT high IT Number Analyzed 247 participants 124 participants 371 participants
23
   9.3%
11
   8.9%
34
   9.2%
Relapse w/I 6 mths after allogeneic HSCT low IT Number Analyzed 247 participants 124 participants 371 participants
16
   6.5%
9
   7.3%
25
   6.7%
Relapse w/I 6 mths after allogeneic HSCT high IT Number Analyzed 247 participants 124 participants 371 participants
15
   6.1%
8
   6.5%
23
   6.2%
Relapse after 6 mths after allogeneic HSCT high IT Number Analyzed 247 participants 124 participants 371 participants
14
   5.7%
7
   5.6%
21
   5.7%
Relapse after 6 mths after CRc and no HSCT low IT Number Analyzed 247 participants 124 participants 371 participants
11
   4.5%
6
   4.8%
17
   4.6%
Relapse after 6 mths after allogeneic HSCT low IT Number Analyzed 247 participants 124 participants 371 participants
3
   1.2%
1
   0.8%
4
   1.1%
[1]
Measure Description: Baseline stratification factors. HSCT is hematopoietic stem cell transplant. CRc is composite complete remission.
1.Primary Outcome
Title Duration of Overall Survival (OS)
Hide Description Overall survival was defined as the time from the date of randomization until the date of death from any cause (death date - randomization date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - randomized date + 1). The date of last contact was the latest date that the participant was known to be alive by the cutoff date. The last contact date was derived for participants alive at the analysis cutoff date. Survival rate and 95% CI were estimated using the Kaplan-Meier method and the Greenwood formula.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the Intention to Treatment (ITT) which consisted of all randomized participants.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 247 124
Median (95% Confidence Interval)
Unit of Measure: Months
9.3
(7.7 to 10.7)
5.6
(4.7 to 7.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments Stratified analysis where tratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments 1-sided P-value
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.637
Confidence Interval (2-Sided) 95%
0.490 to 0.830
Estimation Comments Based on Cox proportional hazards model. Assuming proportional hazards, an HR of < 1 indicates a reduction in the hazard rate in favor of the gilteritinib arm
2.Primary Outcome
Title Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm
Hide Description The CR/CRh rate was defined as the number of participants who achieved either CR or CRh at any of the postbaseline visits divided by the number of participants in the analysis population.
Time Frame From randomization until the data cut-off date 04 Aug 2017, the 142 patients included in the primary analysis of CR/CRh rate were followed up at least 112 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the response analysis set (RAS) which consisted of participants who were who were at least 112 days past the first dose of gilteritinib or randomization (for participants who did not receive gilteritinib). The participants were analyzed based on the randomized treatments.
Arm/Group Title Gilteritinib
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Overall Number of Participants Analyzed 142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
CR/CRh rate
28.2
(20.9 to 36.3)
CR rate
19.0
(12.9 to 26.4)
CRh rate
9.2
(5.0 to 15.1)
3.Secondary Outcome
Title Duration of Event-Free Survival (EFS)
Hide Description EFS was defined as the time from the date of randomization until the date of documented relapse (excluding relapse after PR), treatment failure or death from any cause within 30 days after the last dose of study drug, whichever occurred first (earliest of [relapse date, treatment failure date, death date] - randomization date + 1). If a participant experienced relapse or death within 30 days after the last dose of study drug, the participant was defined as having an EFS event related to either "relapse" or "death", and the event date was the date of relapse or death. For a participant who was not known to have had a relapse or treatment failure or death event, EFS was censored at the date of last relapse-free disease assessment (last relapse-free disease assessment date - randomization date + 1). Data was estimated based on Kaplan-Meier estimates.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 189 62
Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(1.4 to 3.7)
0.7 [1] 
(0.2 to NA)
[1]
Not estimable. Data could not be estimated due to low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0415
Comments 1-sided P-value
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.793
Confidence Interval (2-Sided) 95%
0.577 to 1.089
Estimation Comments Based on the Cox proportional hazards model. Assuming proportional hazards, an HR of < 1 indicates a reduction in the hazard rate in favor of the gilteritinib arm.
4.Secondary Outcome
Title Percentage of Participants With Complete Remission (CR) Rate
Hide Description The CR rate was defined as the number of participants who achieved the best response of CR divided by the number of participants in the analysis population.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, all participants included in the primary analysis of CR rate were followed up at least 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 247 124
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
21.1
(16.1 to 26.7)
10.5
(5.7 to 17.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments Based on stratified Cochran-Mantel-Haenszel test. Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT. Treatment difference = gilteritinib –chemotherapy.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0106
Comments Stratified P-value
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 10.6
Confidence Interval (2-Sided) 95%
2.8 to 18.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Duration of Leukemia-Free Survival (LFS)
Hide Description The LFS was defined as the time from the date of first CRc until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CRc (relapse date or death date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1).
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT, with participants with best response of CRc.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 134 27
Median (95% Confidence Interval)
Unit of Measure: Months
4.4
(3.6 to 5.2)
6.7
(2.1 to 8.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments The LFS was analyzed for participants who achieved remission using the stratified log-rank test with strata to control for response to first-line AML therapy and preselected salvage chemotherapy. Duration of LFS was based on Kaplan-Meier estimates.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6654
Comments Unstratified p-value
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.889
Confidence Interval (2-Sided) 95%
0.506 to 1.563
Estimation Comments Based on the Cox proportional hazards model. Assuming proportional hazards, an HR of < 1 indicates a reduction in the hazard rate in favor of the gilteritinib arm.
6.Secondary Outcome
Title Duration of Remission
Hide Description Duration of remission included duration of composite complete remission (CRc), duration of complete remission (CR)/ complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR and duration of response (CRc + partial remission (PR). The duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse (i.e., the date of first NR after CRc or PR) for participants who achieved CRc or PR (relapse date - first CRc or PR disease assessment date + 1). Participants who died without report of relapse were considered nonevents and censored at their last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc or PR disease assessment date + 1). Other participants who did not relapse during the study were considered nonevents and censored at the last relapse-free assessment date. Duration of CR was only applicable to participants with best overall response of CR.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT, Duration of CR was only applicable to participants with best overall response of CR.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 52 13
Median (95% Confidence Interval)
Unit of Measure: Months
14.8 [1] 
(11.0 to NA)
1.8 [1] 
(NA to NA)
[1]
Not estimable. Data could not be estimated due to low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1189
Comments Unstratified
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.206
Confidence Interval (2-Sided) 95%
0.022 to 1.886
Estimation Comments Based on Cox proportional hazards model. Assuming proportional hazards, a hazard ratio < 1 indicates a reduction in hazard rate in favor of gilteritinib arm.
7.Secondary Outcome
Title Percentage of Participants With Composite Complete Remission (CRc Rate)
Hide Description CRc rate was defined as the number of participants who achieved the best response of CRc (CR,complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi) divided by the number of participants in the analysis population.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 247 124
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
54.3
(47.8 to 60.6)
21.8
(14.9 to 30.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments Treatment difference = gilteritinib – chemotherapy. The 95% CIs were asymptotic confidence limits using the normal approximation to the binomial distribution.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Unstratified 2-sided P-value
Method 2-sided Fisher’s exact test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 32.5
Confidence Interval (2-Sided) 95%
22.3 to 42.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Who Underwent Hematopoietic Stem Cell Transplant
Hide Description Transplantation rate is defined as the percentage of participants undergoing Hematopoietic stem cell transplant (HSCT) during the study period.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population is the ITT.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 247 124
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
25.5
(20.2 to 31.4)
15.3
(9.5 to 22.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0333
Comments Unstratified 2-sided P-value.
Method 2-sided Fisher’s exact test
Comments Treatment difference = gilteritinib – chemotherapy.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 10.2
Confidence Interval (2-Sided) 95%
1.2 to 19.1
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Brief Fatigue Inventory (BFI)
Hide Description The Brief Fatigue Inventory (BFI) is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A global fatigue score can be obtained by averaging all the items on the BFI. The global BFI score will be calculated only if at least 5 of the 9 items are answered. A higher BFI fatigue score indicates worse outcome.
Time Frame Baseline and cycle 1, day 8 and cycle 2 day 1 (up to data cut off date of 17 Sep 2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT, with participants with data at baseline.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 227 97
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Cycle 1 day 8 (C1D8) Number Analyzed 191 participants 73 participants
-0.4  (2.1) 1.0  (2.3)
Cycle 2 day 1 (C2D1) Number Analyzed 206 participants 15 participants
0.0  (2.6) 0.4  (2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments C1D8: Using analysis of covariance (ANCOVA) including treatment as a fixed factor, baseline score, response to first-line AML therapy and preselected salvage chemotherapy per IRT as covariates. Least Square (LS) Mean difference was estimated using chemotherapy as control.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.2567
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments C2D1: Using analysis of covariance (ANCOVA) including treatment as a fixed factor, baseline score, response to first-line AML therapy and preselected salvage chemotherapy per IRT as covariates. Least Square (LS) Mean difference was estimated using chemotherapy as control.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8037
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.1574
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Complete Remission (CR) With Partial Hematological Recovery (CRh)
Hide Description CRh rate was defined as the number of participants who achieved CRh at any of the postbaseline visits and did not have a best response of CR divided by the number of participants in the analysis population.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT.
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 247 124
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
34.0
(28.1 to 40.3)
15.3
(9.5 to 22.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib, Salvage Chemotherapy
Comments

Based on a stratified Cochran-Mantel-Haenszel test. Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT. Pooled strata were used as shown in Table 12.3.3.2.

Treatment differences were adjusted based on pooled strata. Treatment difference = gilteritinib 120 mg – chemotherapy.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0171
Comments Stratified 1-sided P-value.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference,
Estimated Value 18.6
Confidence Interval (2-Sided) 95%
9.8 to 27.4
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants Who Achieved Transfusion Conversion and Maintenance
Hide Description Transfusion conversion & maintenance rate was defined for gilteritinib arm. Participants were classified as transfusion independent if there were no RBC or platelet transfusions within 28 days prior to the first dose to 28 days after the first dose; otherwise they were classified as transfusion dependent at baseline. Participants were considered independent postbaseline if they had 1 consecutive 8 week period without any RBC or platelet transfusion from 29 days after the first dose until the last dose date. For participants who were on treatment ≤ 4 weeks or > 4 weeks but < 12 weeks and there was no RBC or platelet transfusion within postbaseline period, they were considered not evaluable; otherwise, they were considered postbaseline transfusion dependent. Transfusion conversion rate was defined for participants who had evaluable postbaseline transfusion status. Transfusion status (independent vs. dependent) at baseline and postbaseline was reported in a 2 by 2 contingency table.
Time Frame From randomization until the data cut-off date of 17 Sep 2018, median treatment duration for gilteritinib was (126.00 [4.0, 885.0]) days versus salvage chemotherapy 28.0 [5.0, 217.0] days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT, with participants who had evaluable postbaseline transfusion status.
Arm/Group Title Gilteritinib
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Overall Number of Participants Analyzed 246
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline Independent/ Post baseline Independent 59.2
Baseline Independent/Post baseline Dependent 24.5
Baseline Independent/Post baseline Not Evaluable 16.3
Baseline Dependent/Post baseline Independent 34.5
Baseline Dependent/Post baseline Dependent 55.8
Baseline Dependent/Post baseline Not Evaluable 9.6
12.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description A treatment-emergent adverse event (TEAE) was defined as an AE observed after starting administration of the study drug (gilteritinib or salvage chemotherapy). If the AE occurred on day 1 and the onset check box was marked "Onset after first dose of study drug" or the onset check box was left blank, then the AE was considered treatment emergent. If the AE occurred on day 1 and the onset check box was marked "Onset before first dose of study drug", then the AE was not considered treatment emergent. Majority of salvage chemotherapy participants finished the study by cycle 2 of treatment, the duration of exposure was longer in the gilteritinib arm compared with the salvage chemotherapy arm (126.00 [4.0, 885.0] days versus 28.0 [5.0, 217.0] days). The NCI-CTCAE is defined as National Cancer Institute-Common Terminology Criteria for Adverse Events.
Time Frame From first dose of study drug up to 30 days after the last dose of study drug (median treatment duration for gilteritinib was (126.00 [4.0, 885.0]) days versus salvage chemotherapy 28.0 [5.0, 217.0] days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the safety analysis set (SAF), which consisted of participants who received who received at least 1 dose of study drug (gilteritinib or salvage chemotherapy).
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description:
Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.
Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
Overall Number of Participants Analyzed 246 109
Measure Type: Count of Participants
Unit of Measure: Participants
Drug-related TEAE
206
  83.7%
71
  65.1%
Serious TEAE
205
  83.3%
34
  31.2%
Drug-related serious TEAE
88
  35.8%
16
  14.7%
TEAE leading to death
71
  28.9%
16
  14.7%
Drug-related TEAE leading to death
10
   4.1%
5
   4.6%
TEAE leading to withdrawal of treatment
58
  23.6%
13
  11.9%
Drug-related TEAE lead withdrawal of treatment
27
  11.0%
5
   4.6%
NCI-CTCAE Grade 3 or higher TEAE
236
  95.9%
94
  86.2%
Drug-related Grade 3 or higher TEAE
153
  62.2%
57
  52.3%
Death
170
  69.1%
81
  74.3%
Time Frame From first dose of study drug up to 30 days after the last dose of study drug (median treatment duration for gilteritinib was (126.00 [4.0, 885.0]) days versus salvage chemotherapy 28.0 [5.0, 217.0] days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Gilteritinib Salvage Chemotherapy
Hide Arm/Group Description Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria. Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.
All-Cause Mortality
Gilteritinib Salvage Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   170/246 (69.11%)      81/109 (74.31%)    
Hide Serious Adverse Events
Gilteritinib Salvage Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   205/246 (83.33%)      34/109 (31.19%)    
Blood and lymphatic system disorders     
Anaemia  1  8/246 (3.25%)  10 0/109 (0.00%)  0
Aplasia pure red cell  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Autoimmune haemolytic anaemia  1  1/246 (0.41%)  3 0/109 (0.00%)  0
Bone marrow failure  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Disseminated intravascular coagulation  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Febrile neutropenia  1  76/246 (30.89%)  112 9/109 (8.26%)  15
Haemolytic anaemia  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Leukocytosis  1  2/246 (0.81%)  2 1/109 (0.92%)  1
Neutropenia  1  3/246 (1.22%)  4 1/109 (0.92%)  1
Pancytopenia  1  4/246 (1.63%)  4 0/109 (0.00%)  0
Thrombocytopenia  1  4/246 (1.63%)  4 1/109 (0.92%)  1
Cardiac disorders     
Acute coronary syndrome  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Angina pectoris  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Atrial fibrillation  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Cardiac arrest  1  4/246 (1.63%)  5 0/109 (0.00%)  0
Cardiac failure  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Cardiac failure congestive  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Cardio-respiratory arrest  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Myocardial infarction  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Myocarditis  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Pericardial effusion  1  3/246 (1.22%)  5 0/109 (0.00%)  0
Pericardial haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pericarditis  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Sinus tachycardia  1  1/246 (0.41%)  1 1/109 (0.92%)  1
Supraventricular tachycardia  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Congenital, familial and genetic disorders     
Hamartoma  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Eye disorders     
Ocular hyperaemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Vision blurred  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Anal fissure  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Colitis  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Diarrhoea  1  10/246 (4.07%)  13 0/109 (0.00%)  0
Diarrhoea haemorrhagic  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Dysphagia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Enterocolitis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Gastritis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Gastrointestinal haemorrhage  1  1/246 (0.41%)  1 1/109 (0.92%)  2
Gastrooesophageal reflux disease  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Haematemesis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Haematochezia  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Haemorrhoids  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Ileus  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Intestinal ischaemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Large intestine perforation  1  2/246 (0.81%)  4 0/109 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Melaena  1  1/246 (0.41%)  1 1/109 (0.92%)  1
Mouth haemorrhage  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Nausea  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Pancreatitis  1  3/246 (1.22%)  4 0/109 (0.00%)  0
Proctalgia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Stomatitis  1  1/246 (0.41%)  1 1/109 (0.92%)  1
Stomatitis necrotising  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Tongue haematoma  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Vomiting  1  1/246 (0.41%)  1 0/109 (0.00%)  0
General disorders     
Asthenia  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Chills  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Death  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Face oedema  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Fatigue  1  4/246 (1.63%)  4 1/109 (0.92%)  1
Generalised oedema  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Influenza like illness  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Mucosal haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Mucosal inflammation  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Multiple organ dysfunction syndrome  1  1/246 (0.41%)  1 1/109 (0.92%)  1
Oedema  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pyrexia  1  32/246 (13.01%)  43 1/109 (0.92%)  2
Hepatobiliary disorders     
Cholecystitis  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Drug-induced liver injury  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hepatic function abnormal  1  1/246 (0.41%)  7 0/109 (0.00%)  0
Hepatotoxicity  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Immune system disorders     
Acute graft versus host disease in intestine  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Anaphylactic reaction  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Drug hypersensitivity  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Graft versus host disease  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Graft versus host disease in gastrointestinal tract  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Infections and infestations     
Abscess bacterial  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Adenoviral upper respiratory infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Anal abscess  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Bacteraemia  1  10/246 (4.07%)  11 1/109 (0.92%)  1
Bacterial colitis  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Bacterial infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Bacterial sepsis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Bronchitis  1  4/246 (1.63%)  5 0/109 (0.00%)  0
Bronchopulmonary aspergillosis  1  2/246 (0.81%)  4 0/109 (0.00%)  0
Catheter site infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Cellulitis  1  6/246 (2.44%)  6 0/109 (0.00%)  0
Clostridium difficile colitis  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Clostridium difficile infection  1  4/246 (1.63%)  4 0/109 (0.00%)  0
Cytomegalovirus infection  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Device related infection  1  4/246 (1.63%)  4 1/109 (0.92%)  1
Diarrhoea infectious  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Endocarditis  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Enterococcal bacteraemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Enterococcal sepsis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Enterocolitis infectious  1  4/246 (1.63%)  5 0/109 (0.00%)  0
Epstein-Barr viraemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Escherichia bacteraemia  1  2/246 (0.81%)  4 0/109 (0.00%)  0
Escherichia sepsis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Escherichia urinary tract infection  1  3/246 (1.22%)  3 1/109 (0.92%)  1
Eye infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Eye infection bacterial  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Haemophilus infection  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Hepatic infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Infection  1  1/246 (0.41%)  3 1/109 (0.92%)  2
Infectious colitis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Influenza  1  3/246 (1.22%)  3 1/109 (0.92%)  2
Klebsiella bacteraemia  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Leptotrichia infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Lower respiratory tract infection  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Lower respiratory tract infection bacterial  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Lower respiratory tract infection fungal  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Lung infection  1  14/246 (5.69%)  17 5/109 (4.59%)  6
Oesophageal infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Otitis externa  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Parotitis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Periorbital infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pneumonia  1  26/246 (10.57%)  40 4/109 (3.67%)  6
Pneumonia fungal  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Pneumonia respiratory syncytial viral  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pneumonia viral  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pseudomonal bacteraemia  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Pseudomonal sepsis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pulmonary mycosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Respiratory syncytial virus infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Respiratory tract infection  1  4/246 (1.63%)  6 0/109 (0.00%)  0
Scrotal infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Sepsis  1  18/246 (7.32%)  23 7/109 (6.42%)  11
Septic shock  1  9/246 (3.66%)  15 1/109 (0.92%)  1
Sinusitis  1  3/246 (1.22%)  4 0/109 (0.00%)  0
Sinusitis fungal  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Skin infection  1  4/246 (1.63%)  7 0/109 (0.00%)  0
Soft tissue infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Staphylococcal bacteraemia  1  6/246 (2.44%)  6 0/109 (0.00%)  0
Staphylococcal infection  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Streptococcal bacteraemia  1  3/246 (1.22%)  4 0/109 (0.00%)  0
Systemic bacterial infection  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Systemic mycosis  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Tooth abscess  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Tooth infection  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Upper respiratory tract infection  1  3/246 (1.22%)  4 0/109 (0.00%)  0
Urinary tract infection  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Urinary tract infection bacterial  1  2/246 (0.81%)  2 1/109 (0.92%)  1
Urinary tract infection enterococcal  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Viral upper respiratory tract infection  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Vulval cellulitis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Wound infection  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Injury, poisoning and procedural complications     
Accidental overdose  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Anaphylactic transfusion reaction  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Ankle fracture  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Fall  1  8/246 (3.25%)  8 1/109 (0.92%)  1
Hip fracture  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Infusion related reaction  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Joint dislocation  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Patella fracture  1  1/246 (0.41%)  2 0/109 (0.00%)  0
Subarachnoid haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Subdural haematoma  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Subdural haemorrhage  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Toxicity to various agents  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  13/246 (5.28%)  17 0/109 (0.00%)  0
Aspartate aminotransferase increased  1  10/246 (4.07%)  14 0/109 (0.00%)  0
Blood alkaline phosphatase increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Blood bilirubin increased  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Blood creatine phosphokinase increased  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Blood creatinine increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Blood fibrinogen decreased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Blood pressure decreased  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Ejection fraction decreased  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Electrocardiogram QT prolonged  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Gamma-glutamyltransferase increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
General physical condition abnormal  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Liver function test increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Menstruation normal  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Neutrophil count decreased  1  4/246 (1.63%)  6 0/109 (0.00%)  0
Norovirus test positive  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Platelet count decreased  1  5/246 (2.03%)  11 0/109 (0.00%)  0
Transaminases increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
White blood cell count decreased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
White blood cell count increased  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Dehydration  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Failure to thrive  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hyperglycaemia  1  0/246 (0.00%)  0 1/109 (0.92%)  2
Hyperphosphataemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hypoglycaemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hypokalaemia  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Hyponatraemia  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Hyponatraemic syndrome  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hypophosphataemia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Metabolic acidosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Tumour lysis syndrome  1  1/246 (0.41%)  1 2/109 (1.83%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Arthritis  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Back pain  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Bone pain  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Joint effusion  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Joint swelling  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Muscular weakness  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Myositis  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Osteoarthritis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pain in extremity  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Pain in jaw  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Soft tissue necrosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  33/246 (13.41%)  38 4/109 (3.67%)  6
Acute myeloid leukaemia recurrent  1  7/246 (2.85%)  9 0/109 (0.00%)  0
Cancer pain  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Central nervous system leukaemia  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Gastric cancer  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Leukaemia cutis  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Leukaemia recurrent  1  1/246 (0.41%)  1 1/109 (0.92%)  2
Malignant neoplasm progression  1  0/246 (0.00%)  0 1/109 (0.92%)  2
Neoplasm malignant  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Oesophageal carcinoma  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Soft tissue sarcoma  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Squamous cell carcinoma  1  0/246 (0.00%)  0 1/109 (0.92%)  2
Nervous system disorders     
Amnesia  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Brain oedema  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Cerebellar haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Cerebral haemorrhage  1  3/246 (1.22%)  3 0/109 (0.00%)  0
Cerebral infarction  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Cerebrovascular accident  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Cognitive disorder  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Depressed level of consciousness  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Dizziness  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Haemorrhage intracranial  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Haemorrhagic stroke  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Headache  1  5/246 (2.03%)  5 0/109 (0.00%)  0
Hemiplegia  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hydrocephalus  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Presyncope  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Seizure  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Somnolence  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Syncope  1  7/246 (2.85%)  8 0/109 (0.00%)  0
Tremor  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Psychiatric disorders     
Confusional state  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Depression  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Hallucination  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Mania  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Mental status changes  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  16/246 (6.50%)  20 4/109 (3.67%)  5
Haematuria  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Renal impairment  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Reproductive system and breast disorders     
Pelvic pain  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Vaginal haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  4/246 (1.63%)  4 0/109 (0.00%)  0
Acute respiratory failure  1  2/246 (0.81%)  2 1/109 (0.92%)  1
Aspiration  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Cough  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Dyspnoea  1  10/246 (4.07%)  10 2/109 (1.83%)  2
Hypoxia  1  4/246 (1.63%)  4 2/109 (1.83%)  2
Interstitial lung disease  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Lung disorder  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Organising pneumonia  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Oropharyngeal pain  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pleural effusion  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Pneumomediastinum  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pneumonia aspiration  1  2/246 (0.81%)  3 0/109 (0.00%)  0
Pneumothorax  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Productive cough  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Pulmonary alveolar haemorrhage  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Pulmonary embolism  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Pulmonary haemorrhage  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Pulmonary hypertension  1  2/246 (0.81%)  2 0/109 (0.00%)  0
Respiratory failure  1  7/246 (2.85%)  8 3/109 (2.75%)  5
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Dermatitis bullous  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Drug eruption  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Petechiae  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Psoriasis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Skin necrosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Swelling face  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Toxic skin eruption  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  0/246 (0.00%)  0 1/109 (0.92%)  1
Embolism  1  3/246 (1.22%)  3 1/109 (0.92%)  1
Haematoma  1  3/246 (1.22%)  5 0/109 (0.00%)  0
Haemorrhage  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Hypertension  1  1/246 (0.41%)  1 1/109 (0.92%)  1
Hypotension  1  6/246 (2.44%)  6 1/109 (0.92%)  1
Orthostatic hypotension  1  1/246 (0.41%)  1 0/109 (0.00%)  0
Venous thrombosis  1  1/246 (0.41%)  1 0/109 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gilteritinib Salvage Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   242/246 (98.37%)      103/109 (94.50%)    
Blood and lymphatic system disorders     
Anaemia  1  110/246 (44.72%)  471 38/109 (34.86%)  80
Disseminated intravascular coagulation  1  7/246 (2.85%)  8 6/109 (5.50%)  6
Febrile neutropenia  1  57/246 (23.17%)  72 32/109 (29.36%)  37
Neutropenia  1  31/246 (12.60%)  105 16/109 (14.68%)  18
Thrombocytopenia  1  62/246 (25.20%)  294 17/109 (15.60%)  41
Cardiac disorders     
Tachycardia  1  12/246 (4.88%)  13 7/109 (6.42%)  7
Eye disorders     
Dry eye  1  24/246 (9.76%)  25 3/109 (2.75%)  3
Retinal haemorrhage  1  19/246 (7.72%)  22 2/109 (1.83%)  2
Vision blurred  1  20/246 (8.13%)  22 1/109 (0.92%)  1
Gastrointestinal disorders     
Abdominal pain  1  36/246 (14.63%)  42 16/109 (14.68%)  17
Constipation  1  76/246 (30.89%)  94 16/109 (14.68%)  18
Diarrhoea  1  79/246 (32.11%)  123 32/109 (29.36%)  37
Dry mouth  1  20/246 (8.13%)  21 3/109 (2.75%)  3
Dyspepsia  1  13/246 (5.28%)  16 7/109 (6.42%)  7
Mouth ulceration  1  13/246 (5.28%)  14 2/109 (1.83%)  2
Nausea  1  79/246 (32.11%)  120 36/109 (33.03%)  41
Stomatitis  1  34/246 (13.82%)  44 15/109 (13.76%)  19
Vomiting  1  53/246 (21.54%)  79 15/109 (13.76%)  16
General disorders     
Asthenia  1  36/246 (14.63%)  50 10/109 (9.17%)  11
Chills  1  22/246 (8.94%)  32 8/109 (7.34%)  9
Fatigue  1  70/246 (28.46%)  98 14/109 (12.84%)  17
Mucosal inflammation  1  13/246 (5.28%)  13 9/109 (8.26%)  11
Oedema  1  15/246 (6.10%)  18 3/109 (2.75%)  3
Oedema peripheral  1  59/246 (23.98%)  77 13/109 (11.93%)  19
Pain  1  17/246 (6.91%)  21 1/109 (0.92%)  1
Pyrexia  1  89/246 (36.18%)  136 31/109 (28.44%)  57
Immune system disorders     
Graft versus host disease  1  13/246 (5.28%)  18 1/109 (0.92%)  1
Infections and infestations     
Cellulitis  1  15/246 (6.10%)  17 1/109 (0.92%)  2
Lung infection  1  14/246 (5.69%)  15 0/109 (0.00%)  0
Pneumonia  1  23/246 (9.35%)  26 5/109 (4.59%)  5
Sinusitis  1  13/246 (5.28%)  18 2/109 (1.83%)  3
Upper respiratory tract infection  1  19/246 (7.72%)  32 3/109 (2.75%)  3
Injury, poisoning and procedural complications     
Allergic transfusion reaction  1  10/246 (4.07%)  17 7/109 (6.42%)  13
Contusion  1  14/246 (5.69%)  16 3/109 (2.75%)  3
Fall  1  18/246 (7.32%)  27 1/109 (0.92%)  1
Investigations     
Alanine aminotransferase increased  1  99/246 (40.24%)  230 10/109 (9.17%)  20
Aspartate aminotransferase increased  1  96/246 (39.02%)  237 13/109 (11.93%)  21
Blood alkaline phosphatase increased  1  55/246 (22.36%)  112 2/109 (1.83%)  2
Blood bilirubin increased  1  21/246 (8.54%)  68 7/109 (6.42%)  9
Blood creatine phosphokinase increased  1  33/246 (13.41%)  94 0/109 (0.00%)  0
Blood creatinine increased  1  29/246 (11.79%)  64 4/109 (3.67%)  4
Blood lactate dehydrogenase increased  1  22/246 (8.94%)  33 5/109 (4.59%)  5
Electrocardiogram QT prolonged  1  16/246 (6.50%)  19 0/109 (0.00%)  0
International normalised ratio increased  1  13/246 (5.28%)  17 5/109 (4.59%)  6
Neutrophil count decreased  1  40/246 (16.26%)  161 12/109 (11.01%)  28
Platelet count decreased  1  53/246 (21.54%)  245 28/109 (25.69%)  76
Weight decreased  1  13/246 (5.28%)  21 3/109 (2.75%)  4
Weight increased  1  13/246 (5.28%)  17 2/109 (1.83%)  6
White blood cell count decreased  1  34/246 (13.82%)  127 19/109 (17.43%)  27
Metabolism and nutrition disorders     
Decreased appetite  1  44/246 (17.89%)  52 20/109 (18.35%)  22
Dehydration  1  13/246 (5.28%)  15 1/109 (0.92%)  1
Hyperglycaemia  1  36/246 (14.63%)  62 13/109 (11.93%)  18
Hyperkalaemia  1  22/246 (8.94%)  32 1/109 (0.92%)  1
Hyperuricaemia  1  23/246 (9.35%)  30 2/109 (1.83%)  2
Hypoalbuminaemia  1  32/246 (13.01%)  64 7/109 (6.42%)  11
Hypocalcaemia  1  47/246 (19.11%)  110 6/109 (5.50%)  14
Hypokalaemia  1  71/246 (28.86%)  183 33/109 (30.28%)  48
Hypomagnesaemia  1  39/246 (15.85%)  67 12/109 (11.01%)  15
Hyponatraemia  1  32/246 (13.01%)  78 6/109 (5.50%)  7
Hypophosphataemia  1  40/246 (16.26%)  69 5/109 (4.59%)  5
Musculoskeletal and connective tissue disorders     
Arthralgia  1  28/246 (11.38%)  42 6/109 (5.50%)  8
Back pain  1  29/246 (11.79%)  32 13/109 (11.93%)  13
Muscular weakness  1  19/246 (7.72%)  22 1/109 (0.92%)  2
Myalgia  1  35/246 (14.23%)  45 4/109 (3.67%)  4
Pain in extremity  1  36/246 (14.63%)  44 8/109 (7.34%)  11
Nervous system disorders     
Dizziness  1  48/246 (19.51%)  64 2/109 (1.83%)  2
Dysgeusia  1  25/246 (10.16%)  28 5/109 (4.59%)  5
Headache  1  61/246 (24.80%)  87 16/109 (14.68%)  18
Paraesthesia  1  21/246 (8.54%)  25 0/109 (0.00%)  0
Psychiatric disorders     
Anxiety  1  19/246 (7.72%)  21 1/109 (0.92%)  1
Depression  1  11/246 (4.47%)  12 7/109 (6.42%)  7
Insomnia  1  40/246 (16.26%)  44 6/109 (5.50%)  6
Renal and urinary disorders     
Haematuria  1  19/246 (7.72%)  21 5/109 (4.59%)  6
Respiratory, thoracic and mediastinal disorders     
Cough  1  70/246 (28.46%)  96 11/109 (10.09%)  13
Dyspnoea  1  50/246 (20.33%)  67 7/109 (6.42%)  8
Dyspnoea exertional  1  15/246 (6.10%)  18 0/109 (0.00%)  0
Epistaxis  1  42/246 (17.07%)  51 8/109 (7.34%)  8
Nasal congestion  1  17/246 (6.91%)  20 1/109 (0.92%)  1
Oropharyngeal pain  1  21/246 (8.54%)  24 8/109 (7.34%)  8
Pleural effusion  1  16/246 (6.50%)  17 2/109 (1.83%)  3
Productive cough  1  16/246 (6.50%)  20 2/109 (1.83%)  2
Skin and subcutaneous tissue disorders     
Dry skin  1  15/246 (6.10%)  19 3/109 (2.75%)  3
Erythema  1  13/246 (5.28%)  16 4/109 (3.67%)  4
Pruritus  1  24/246 (9.76%)  29 3/109 (2.75%)  3
Rash  1  36/246 (14.63%)  48 10/109 (9.17%)  10
Rash maculo-papular  1  10/246 (4.07%)  13 6/109 (5.50%)  6
Vascular disorders     
Hypertension  1  33/246 (13.41%)  56 10/109 (9.17%)  10
Hypotension  1  38/246 (15.45%)  44 7/109 (6.42%)  8
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
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.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosure
Organization: Astellas Pharma Global Development, Inc.
Phone: 800-888-7704
EMail: astellas.resultsdisclosure@astellas.com
Layout table for additonal information
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT02421939    
Other Study ID Numbers: 2215-CL-0301
2015-000140-42 ( EudraCT Number )
First Submitted: April 16, 2015
First Posted: April 21, 2015
Results First Submitted: September 12, 2019
Results First Posted: October 17, 2019
Last Update Posted: March 16, 2020