Trial Outcomes & Findings for A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (NCT NCT02421939)

NCT ID: NCT02421939

Last Updated: 2025-12-04

Results Overview

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. 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

371 participants

Primary outcome timeframe

From randomization to until the date of death from any cause (median time of follow-up for OS was 17.8 months)

Results posted on

2025-12-04

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Gilteritinib 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Randomization Period: Up to 3 Years STARTED	247	124
Randomization Period: Up to 3 Years Treated	246	109
Randomization Period: Up to 3 Years COMPLETED	0	19
Randomization Period: Up to 3 Years NOT COMPLETED	247	105
Long Term Follow up: up to 3 Years STARTED	133	73
Long Term Follow up: up to 3 Years COMPLETED	0	0
Long Term Follow up: up to 3 Years NOT COMPLETED	133	73

Reasons for withdrawal

Reasons for withdrawal
Measure	Gilteritinib 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Randomization Period: Up to 3 Years Progressive disease	76	16
Randomization Period: Up to 3 Years Lack of Efficacy	21	31
Randomization Period: Up to 3 Years Death	38	10
Randomization Period: Up to 3 Years Disease relapse	37	2
Randomization Period: Up to 3 Years Adverse Event	32	5
Randomization Period: Up to 3 Years Withdrawal by Subject	9	24
Randomization Period: Up to 3 Years Physician Decision	13	11
Randomization Period: Up to 3 Years Protocol deviation	1	1
Randomization Period: Up to 3 Years Miscellaneous	20	5
Long Term Follow up: up to 3 Years Withdrawal by Subject	4	5
Long Term Follow up: up to 3 Years Lost to Follow-up	1	2
Long Term Follow up: up to 3 Years Death	118	65
Long Term Follow up: up to 3 Years Miscellaneous	10	1

Baseline Characteristics

The analysis population was the ITT, with available data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).	Total n=371 Participants Total of all reporting groups
Age, Continuous	59 Years STANDARD_DEVIATION 14.6 • n=247 Participants	57.6 Years STANDARD_DEVIATION 14.8 • n=124 Participants	58.5 Years STANDARD_DEVIATION 14.7 • n=371 Participants
Sex: Female, Male Female	131 Participants n=247 Participants	70 Participants n=124 Participants	201 Participants n=371 Participants
Sex: Female, Male Male	116 Participants n=247 Participants	54 Participants n=124 Participants	170 Participants n=371 Participants
Race/Ethnicity, Customized WHITE	145 Participants n=247 Participants	75 Participants n=124 Participants	220 Participants n=371 Participants
Race/Ethnicity, Customized ASIAN	69 Participants n=247 Participants	33 Participants n=124 Participants	102 Participants n=371 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	14 Participants n=247 Participants	7 Participants n=124 Participants	21 Participants n=371 Participants
Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	1 Participants n=247 Participants	0 Participants n=124 Participants	1 Participants n=371 Participants
Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE	0 Participants n=247 Participants	0 Participants n=124 Participants	0 Participants n=371 Participants
Race/Ethnicity, Customized UNKNOWN	4 Participants n=247 Participants	4 Participants n=124 Participants	8 Participants n=371 Participants
Race/Ethnicity, Customized OTHER	5 Participants n=247 Participants	1 Participants n=124 Participants	6 Participants n=371 Participants
Race/Ethnicity, Customized MISSING	9 Participants n=247 Participants	4 Participants n=124 Participants	13 Participants n=371 Participants
Ethnicity NOT HISPANIC OR LATINO	221 Participants n=247 Participants	116 Participants n=124 Participants	337 Participants n=371 Participants
Ethnicity HISPANIC OR LATINO	12 Participants n=247 Participants	2 Participants n=124 Participants	14 Participants n=371 Participants
Ethnicity UNKNOWN	3 Participants n=247 Participants	2 Participants n=124 Participants	5 Participants n=371 Participants
Ethnicity MISSING	11 Participants n=247 Participants	4 Participants n=124 Participants	15 Participants n=371 Participants
Cytogenic Risk Status INTERMEDIATE	182 Participants n=247 Participants	89 Participants n=124 Participants	271 Participants n=371 Participants
Cytogenic Risk Status UNFAVORABLE	26 Participants n=247 Participants	11 Participants n=124 Participants	37 Participants n=371 Participants
Cytogenic Risk Status FAVORABLE	4 Participants n=247 Participants	1 Participants n=124 Participants	5 Participants n=371 Participants
Cytogenic Risk Status OTHER	35 Participants n=247 Participants	23 Participants n=124 Participants	58 Participants n=371 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) 0-1	206 Participants n=247 Participants	105 Participants n=124 Participants	311 Participants n=371 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) >=2	41 Participants n=247 Participants	19 Participants n=124 Participants	60 Participants n=371 Participants
FLT3 Mutation Status by Central Testing by FLT3 CDx FLT3-ITD Alone	215 Participants n=247 Participants	113 Participants n=124 Participants	328 Participants n=371 Participants
FLT3 Mutation Status by Central Testing by FLT3 CDx FLT3-TKD Alone	21 Participants n=247 Participants	10 Participants n=124 Participants	31 Participants n=371 Participants
FLT3 Mutation Status by Central Testing by FLT3 CDx FLT3-ITD and FLT3-TKD	7 Participants n=247 Participants	0 Participants n=124 Participants	7 Participants n=371 Participants
FLT3 Mutation Status by Central Testing by FLT3 CDx Others (Unknown/Missing/Negative)	4 Participants n=247 Participants	1 Participants n=124 Participants	5 Participants n=371 Participants
Prior Use of FLT3 Inhibitor No	215 Participants n=247 Participants	110 Participants n=124 Participants	325 Participants n=371 Participants
Prior Use of FLT3 Inhibitor Yes	32 Participants n=247 Participants	14 Participants n=124 Participants	46 Participants n=371 Participants
Region NORTH AMERICA	114 Participants n=247 Participants	52 Participants n=124 Participants	166 Participants n=371 Participants
Region EUROPE	68 Participants n=247 Participants	43 Participants n=124 Participants	111 Participants n=371 Participants
Region ASIA	65 Participants n=247 Participants	29 Participants n=124 Participants	94 Participants n=371 Participants
Baseline Body Surface Area (BSA)	1.815 m^2 STANDARD_DEVIATION 0.281 • n=199 Participants • The analysis population was the ITT, with available data.	1.777 m^2 STANDARD_DEVIATION 0.257 • n=122 Participants • The analysis population was the ITT, with available data.	1.8 m^2 STANDARD_DEVIATION 0.272 • n=321 Participants • The analysis population was the ITT, with available data.
Baseline Height	167.25 centimeter (cm) STANDARD_DEVIATION 10.31 • n=234 Participants • The analysis population was the ITT, with available data.	166.39 centimeter (cm) STANDARD_DEVIATION 10.63 • n=123 Participants • The analysis population was the ITT, with available data.	166.95 centimeter (cm) STANDARD_DEVIATION 10.41 • n=357 Participants • The analysis population was the ITT, with available data.
Baseline Weight	72.79 kilogram (kg) STANDARD_DEVIATION 20.47 • n=243 Participants • The analysis population was the ITT, with available data.	69.91 kilogram (kg) STANDARD_DEVIATION 19.73 • n=124 Participants • The analysis population was the ITT, with available data.	71.82 kilogram (kg) STANDARD_DEVIATION 20.25 • n=367 Participants • The analysis population was the ITT, with available data.
Response to First Line Therapy Primary refractory without HSCT	98 Participants n=247 Participants	48 Participants n=124 Participants	146 Participants n=371 Participants
Response to First Line Therapy Relapse within 6 months after CRc and no HSCT	67 Participants n=247 Participants	34 Participants n=124 Participants	101 Participants n=371 Participants
Response to First Line Therapy Relapse after 6 months after CRc and no HSCT	34 Participants n=247 Participants	17 Participants n=124 Participants	51 Participants n=371 Participants
Response to First Line Therapy Relapse within 6 months after allogeneic HSCT	31 Participants n=247 Participants	17 Participants n=124 Participants	48 Participants n=371 Participants
Response to First Line Therapy Relapse after 6 months after allogeneic HSCT	17 Participants n=247 Participants	8 Participants n=124 Participants	25 Participants n=371 Participants
Preselected Salvage Chemotherapy High intensity chemotherapy	149 Participants n=247 Participants	75 Participants n=124 Participants	224 Participants n=371 Participants
Preselected Salvage Chemotherapy Low intensity chemotherapy	98 Participants n=247 Participants	49 Participants n=124 Participants	147 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Primary refractory w/o HSCT, high intensity (IT)	57 Participants n=247 Participants	28 Participants n=124 Participants	85 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Primary refractory w/o HSCT, low IT	41 Participants n=247 Participants	20 Participants n=124 Participants	61 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse w/I 6 mths after CRc and no HSCT, high IT	40 Participants n=247 Participants	21 Participants n=124 Participants	61 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse w/I 6 mths after CRc and no HSCT low IT	27 Participants n=247 Participants	13 Participants n=124 Participants	40 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse after 6 mths after CRc and no HSCT high IT	23 Participants n=247 Participants	11 Participants n=124 Participants	34 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse w/I 6 mths after allogeneic HSCT low IT	16 Participants n=247 Participants	9 Participants n=124 Participants	25 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse w/I 6 mths after allogeneic HSCT high IT	15 Participants n=247 Participants	8 Participants n=124 Participants	23 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse after 6 mths after allogeneic HSCT high IT	14 Participants n=247 Participants	7 Participants n=124 Participants	21 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse after 6 mths after CRc and no HSCT low IT	11 Participants n=247 Participants	6 Participants n=124 Participants	17 Participants n=371 Participants
Response to First Line Therapy-Preselected Salvage Chemotherapy Relapse after 6 mths after allogeneic HSCT low IT	3 Participants n=247 Participants	1 Participants n=124 Participants	4 Participants n=371 Participants

PRIMARY outcome

Timeframe: From randomization to until the date of death from any cause (median time of follow-up for OS was 17.8 months)

Population: The analysis population was the Intention to Treatment (ITT) which consisted of all randomized participants.

Outcome measures

Outcome measures
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Duration of Overall Survival (OS)	9.3 Months Interval 7.7 to 10.7	5.6 Months Interval 4.7 to 7.3

PRIMARY outcome

Timeframe: From the date of randomization up to at least 112 days

Population: 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.

The CR/CRh rate was defined as the number of participants who achieved either CR or CRh divided by the number of participants in the analysis population. CR: For participants to be classified as being in CR at, they must have had bone marrow regenerating normal hematopoietic cells and achieved a morphologic leukemia-free state and must had an ANC ≥ 1 x 10\^9/L and platelet count ≥ 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and they were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There was no evidence of extramedullary leukemia. CRh: Participants were classified as CRh if they had marrow blasts \< 5%, partial hematologic recovery ANC ≥ 0.5 x 10\^9/L and platelets ≥ 50 x 10\^9/L, no evidence of extramedullary leukemia and could not be classified as CR.

Outcome measures

Outcome measures
Measure	Gilteritinib n=142 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm CR/CRh rate	28.2 Percentage of participants Interval 20.9 to 36.3	—
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm CR rate	19.0 Percentage of participants Interval 12.9 to 26.4	—
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm CRh rate	9.2 Percentage of participants Interval 5.0 to 15.1	—

SECONDARY outcome

Timeframe: From the date of randomization until the date of documented relapse, treatment failure or death from any cause (median time of follow-up was 17.8 months)

Population: The analysis population was the ITT with available data.

EFS: time from randomization date up to date of documented relapse (excluding relapse after PR)/ treatment failure (failure to achieve CR, CRp, CRi /PR) /death, whichever occurred first. Relapse: leukemic blasts in peripheral blood 5/ ≥ 25% blasts in bone marrow (BM) aspirate due to no other cause/reappearance/new appearance of extramedullary leukemia. CR: BM regenerating normal hematopoietic cells, morphologic leukemia-free state, ANC ≥1x10\^9/L, platelet count ≥100x10\^9/L, normal marrow differential with \<5% blasts, and RBC/platelet transfusion independent with no extramedullary leukemia. CRp: achieved CR except incomplete platelet recovery (\<100x 0\^9/L). CRi: criteria for CR fulfilled except incomplete hematological recovery with residual neutropenia \<1x10\^9/L with /without complete platelet recovery. PR: BM regenerating normal hematopoietic cells, peripheral recovery, no circulating blasts and decrease of 50% blasts in with total blasts between 5% -25% or, 5% if Auer rods present.

Outcome measures

Outcome measures
Measure	Gilteritinib n=189 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=62 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Duration of Event-Free Survival (EFS)	2.8 Months Interval 1.4 to 3.7	0.7 Months Interval 0.2 to Not estimable. Data could not be estimated due to low number of events.

SECONDARY outcome

Timeframe: From the date of randomization up to at least 6 months

Population: The analysis population was the ITT.

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. CR: For participants to be classified as being in CR, they must have had bone marrow regenerating normal hematopoietic cells and achieved a morphologic leukemia-free state and must had an ANC ≥ 1 x 10\^9/L and platelet count ≥ 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and they were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There was no evidence of extramedullary leukemia.

Outcome measures

Outcome measures
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants With Complete Remission (CR) Rate	21.1 Percentage of participants Interval 16.1 to 26.7	10.5 Percentage of participants Interval 5.7 to 17.3

SECONDARY outcome

Timeframe: From the date of first CRc until the date of documented relapse or death for participants who achieved CRc (median time of follow-up was 17.8 months)

Population: The analysis population was the ITT, with participants with best response of CRc.

LFS: time from the date of first CRc until the date of documented relapse or death for subjects who achieve CRc. For a subject who is not known to have relapsed or died, LFS is censored on the date of last relapse-free disease assessment date. CRc: achieved CR, CRp or CRi. Relapse: leukemic blasts in peripheral blood/ ≥ 25% blasts in bone marrow (BM) aspirate not due to any other cause/reappearance/new appearance of extramedullary leukemia. CR: BM regenerating normal hematopoietic cells, morphologic leukemia-free state, ANC ≥ 1 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, normal marrow differential with \< 5% blasts, and RBC/platelet transfusion independent with no extramedullary leukemia. CRp: achieved CR except incomplete platelet recovery (\< 100 x 10\^9/L). CRi : criteria for CR fulfilled except incomplete hematological recovery with residual neutropenia \< 1 x 10\^9/L with /without complete platelet recovery..

Outcome measures

Outcome measures
Measure	Gilteritinib n=134 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=27 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Duration of Leukemia-Free Survival (LFS)	4.4 Months Interval 3.6 to 5.2	6.7 Months Interval 2.1 to 8.5

SECONDARY outcome

Timeframe: From the date of first response until the date of documented relapse for participants who achieved CRc or PR (median time of follow-up was 17.8 months)

Population: The analysis population was the ITT, Duration of CR was only applicable to participants with best overall response of CR.

Duration of remission included duration of CRc, CR/CRh, CRh, CR, CRi, CRp (defined as the time from the date of first CRc until the date of first documented relapse for participants who achieved CRc, CR/CRh, CRh, CR, CRi, CRp respectively) and duration of response (CRc + PR). CRc: achieved CR, CRp or CRi at the visit. CR: BM regenerating normal hematopoietic cells, morphologic leukemia-free state, ANC ≥1x10\^9/L, platelet count ≥100x10\^9/L, normal marrow differential with \<5% blasts, and RBC/platelet transfusion independent with no extramedullary leukemia. CRp: achieved CR except incomplete platelet recovery (\<100x 0\^9/L). CRi: criteria for CR fulfilled except incomplete hematological recovery with residual neutropenia \<1x10\^9/L with /without complete platelet recovery. PR: BM regenerating normal hematopoietic cells, peripheral recovery, no circulating blasts and decrease of 50% blasts in with total blasts between 5% -25% or, 5% if Auer rods present.

Outcome measures

Outcome measures
Measure	Gilteritinib n=52 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=13 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Duration of Remission	14.8 Months Interval 11.0 to Not estimable. Data could not be estimated due to low number of events.	1.8 Months Not estimable. Data could not be estimated due to low number of events.

SECONDARY outcome

Timeframe: From the date of randomization up to at least 6 months

Population: The analysis population was the ITT.

CRc rate: Number of participants with best response of CRc (CR,complete remission with incomplete platelet recovery \[CRp\] or complete remission with incomplete hematologic recovery \[CRi\]) divided by number of participants in the analysis population. CRc : Participants who achieved CR, CRp or CRi at a post-baseline visit. CR: Participants having bone marrow regenerating normal hematopoietic cells, a morphologic leukemia-free state, an ANC ≥ 1 x 10\^9/L and platelet count ≥ 100 x 10\^9/L, normal marrow differential with \< 5% blasts, and being RBC and platelet transfusion independent with no evidence of extramedullary leukemia at a post-baseline visit. CRp: Participants achieving CR except for incomplete platelet recovery (\< 100 x 10\^9/L) at a post-baseline visit. CRi : Participants, who fulfilled all criteria for CR except incomplete hematological recovery with residual neutropenia \< 1 x 10\^9/L with or without complete platelet recovery at a post-baseline visit.

Outcome measures

Outcome measures
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants With Composite Complete Remission (CRc Rate)	54.3 Percentage of participants Interval 47.8 to 60.6	21.8 Percentage of participants Interval 14.9 to 30.1

SECONDARY outcome

Timeframe: From the date of randomization until end of study (median time of follow-up was 17.8 months)

Population: The analysis population is the ITT.

Transplantation rate is defined as the percentage of participants undergoing Hematopoietic stem cell transplant (HSCT) during the study period.

Outcome measures

Outcome measures
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants Who Underwent Hematopoietic Stem Cell Transplant	25.5 Percentage of participants Interval 20.2 to 31.4	15.3 Percentage of participants Interval 9.5 to 22.9

SECONDARY outcome

Timeframe: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1

Population: The analysis population was the ITT, with participants with data at baseline.

The Brief Fatigue Inventory (BFI) was 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 asked 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 asked 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 total score range is 0-10 with a higher BFI fatigue score indicates worse outcome. The global BFI score was calculated only if at least 5 of the 9 items are answered.

Outcome measures

Outcome measures
Measure	Gilteritinib n=227 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=97 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Change From Baseline in Brief Fatigue Inventory (BFI) Cycle 1 day 8 (C1D8)	-0.4 Units on a scale Standard Deviation 2.1	1.0 Units on a scale Standard Deviation 2.3
Change From Baseline in Brief Fatigue Inventory (BFI) Cycle 2 day 1 (C2D1)	0.0 Units on a scale Standard Deviation 2.6	0.4 Units on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: From the date of randomization up to at least 6 months

Population: The analysis population was the ITT.

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. CR: For participants to be classified as being in CR at a post-baseline visit, they must have had bone marrow regenerating normal hematopoietic cells and achieved a morphologic leukemia-free state and must had an ANC ≥ 1 x 10\^9/L and platelet count ≥ 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and they were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There was no evidence of extramedullary leukemia. CRh: At a post baseline visit, participantss were classified as CRh if they had marrow blasts \< 5%, partial hematologic recovery ANC ≥ 0.5 x 10\^9/L and platelets ≥ 50 x 10\^9/L, no evidence of extramedullary leukemia and could not be classified as CR.

Outcome measures

Outcome measures
Measure	Gilteritinib n=247 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=124 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants With Complete Remission (CR) With Partial Hematological Recovery (CRh)	34.0 Percentage of participants Interval 28.1 to 40.3	15.3 Percentage of participants Interval 9.5 to 22.9

SECONDARY outcome

Timeframe: From 29 days post first dose of study drug until last dose(median treatment duration was (126.00 [4.0, 885.0])

Population: The analysis population was the ITT, with participants who had evaluable postbaseline transfusion status.

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.

Outcome measures

Outcome measures
Measure	Gilteritinib n=246 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Independent/ Post baseline Independent	59.2 Percentage of participants	—
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Independent/Post baseline Dependent	24.5 Percentage of participants	—
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Independent/Post baseline Not Evaluable	16.3 Percentage of participants	—
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Dependent/Post baseline Independent	34.5 Percentage of participants	—
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Dependent/Post baseline Dependent	55.8 Percentage of participants	—
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance Baseline Dependent/Post baseline Not Evaluable	9.6 Percentage of participants	—

SECONDARY outcome

Timeframe: 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)

Population: 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).

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study drug, whether or not related to it. It could be any unfavorable/unintended sign (including abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with use of the study drug. A treatment-emergent adverse event (TEAE) : AEs observed after starting administration of study drug (gilteritinib or salvage chemotherapy). Serious AEs (SAEs): AEs which caused death, were life-threatening, resulted in persistent/significant disability/incapacity or disruption of the ability to conduct normal life functions, congenital anomaly, birth defect, required inpatient hospitalization/led to prolongation of hospitalization. Based on national cancer institute common terminology criteria (NCI-CTCAE), AEs were graded as grade 1=mild, grade 2=moderate, grade 3 =severe or medically significant, grade 4 =life threatening, grade 5 =death related to AE

Outcome measures

Outcome measures
Measure	Gilteritinib n=246 Participants 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. After the end of treatment period, participants were allowed to enter long-term follow up period for up to 3 years for collection of subsequent AML treatment, EuroQol Group-5 Dimension-5 Level Instrument (EQ-5D-5L), remission status and survival (cause of death and date of death). Participants continuing to derive clinical benefit from gilteritinib as assessed by the investigator were allowed to continue the study treatment until a discontinuation criterion was met or if they had completed more than 3 years of treatment.	Salvage Chemotherapy n=109 Participants 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 mitoxantrone, etoposide and intermediate-dose cytarabine (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 fludarabine, cytarabine and granulocyte colony-stimulating factor with idarubicin (FLAG-IDA) chemotherapy received granulocyte-colony stimulating factor (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. After the end of treatment period, participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death).
Number of Participants With Treatment Emergent Adverse Events Drug-related TEAE	208 Participants	71 Participants
Number of Participants With Treatment Emergent Adverse Events Serious TEAE	211 Participants	34 Participants
Number of Participants With Treatment Emergent Adverse Events Drug-related serious TEAE	92 Participants	16 Participants
Number of Participants With Treatment Emergent Adverse Events TEAE leading to death	76 Participants	16 Participants
Number of Participants With Treatment Emergent Adverse Events Drug-related TEAE leading to death	11 Participants	5 Participants
Number of Participants With Treatment Emergent Adverse Events TEAE leading to withdrawal of treatment	65 Participants	13 Participants
Number of Participants With Treatment Emergent Adverse Events Drug-related TEAE lead withdrawal of treatment	30 Participants	5 Participants
Number of Participants With Treatment Emergent Adverse Events NCI-CTCAE Grade 3 or higher TEAE	238 Participants	94 Participants
Number of Participants With Treatment Emergent Adverse Events Drug-related Grade 3 or higher TEAE	157 Participants	57 Participants
Number of Participants With Treatment Emergent Adverse Events Death	203 Participants	87 Participants

Adverse Events

Gilteritinib

Serious events: 211 serious events

Other events: 242 other events

Deaths: 204 deaths

Salvage Chemotherapy

Serious events: 34 serious events

Other events: 103 other events

Deaths: 96 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc.

Phone: 800-888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER