Trial Outcomes & Findings for Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (NCT NCT03836209)

Last Updated: 2025-06-15

Results Overview

FLT3 mutation negative (evaluated by polymerase chain reaction \[PCR\]) Composite Complete Response (CRc) \[includes CR and CRi\] rate after induction treatment and complete MRD assessment. The cut points used for FLT3 mutation negative are 1% (equivalent to 10-2) for FLT3-TKD and 10-4 for FLT3-ITD.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

181 participants

Primary outcome timeframe

3 months

Results posted on

2025-06-15

Participant Flow

All randomized, eligible, and treated patients. 3 patients passed away/withdrew before induction. 1 patient determined to not have the diagnosis to meet the eligibility criteria and was removed from the study (181 consented).

Participant milestones

Participant milestones
Measure	Arm A Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Overall Study STARTED	90	87
Overall Study COMPLETED	10	6
Overall Study NOT COMPLETED	80	81

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Overall Study Adverse Event	5	2
Overall Study Death	4	1
Overall Study Lack of Efficacy	7	10
Overall Study Physician Decision	7	11
Overall Study Protocol Violation	0	3
Overall Study Withdrawal by Subject	2	10
Overall Study Intercurrent illness, Recurrence of disease, Subject proceeded to transplant or non-protocol therapy	55	44

Baseline Characteristics

Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Total n=177 Participants Total of all reporting groups
Age, Continuous	50 years STANDARD_DEVIATION 13 • n=5 Participants	51 years STANDARD_DEVIATION 12 • n=7 Participants	51 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	54 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	33 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=5 Participants	77 Participants n=7 Participants	152 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	68 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Score 0	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Score 1	58 Participants n=5 Participants	56 Participants n=7 Participants	114 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Score 2	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Score 3	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Score Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
AML Category AML with Myelodysplasia-Related Changes	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
AML Category De Novo AML	80 Participants n=5 Participants	79 Participants n=7 Participants	159 Participants n=5 Participants
AML Category Therapy-Related AML	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
WHO Classification AML related to previous chemotherapy or radiation	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
WHO Classification AML with certain genetic abnormalities	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
WHO Classification AML with myelodysplasia-related changes	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
WHO Classification AML not otherwise specified	50 Participants n=5 Participants	50 Participants n=7 Participants	100 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Outcome measures

Outcome measures
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
FLT3 Mutation Negative Composite Complete Response (CRc) [Includes Complete Response (CR) or CR With Incomplete Hematologic Recovery (CRi)] at End of Induction	36 Participants	41 Participants

SECONDARY outcome

Timeframe: 3 months

CR evaluated by FLT3 testing after Induction

Outcome measures

Outcome measures
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
FLT3 Mutation Negative Complete Response (CR) Rate at End of Induction	33 Participants	37 Participants

SECONDARY outcome

Timeframe: 3 months

MRD- CRc evaluated by flow cytometry after Induction

Outcome measures

Outcome measures
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Minimal Residual Disease (MRD)- CRc Rate at End of Induction	58 Participants	52 Participants

SECONDARY outcome

Timeframe: 3 months

CRc assessed in accordance with 2017 European LeukemiaNet (ELN)

Outcome measures

Outcome measures
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
CRc (CR or CRi) Rate at End of Induction	77 Participants	63 Participants

SECONDARY outcome

Timeframe: 68 months

EFS assessed in accordance with 2017 ELN

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 68 months

OS assessed in accordance with 2017 ELN

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 months

Number of participants with abnormal laboratory values and/or adverse events

Outcome measures

Outcome measures
Measure	Arm A n=90 Participants Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 Participants Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Number of Participants Treatment-related Adverse Events as Assessed by CTCAE v5.0	82 Participants	73 Participants

Adverse Events

Arm A

Serious events: 48 serious events

Other events: 83 other events

Deaths: 23 deaths

Arm B

Serious events: 39 serious events

Other events: 81 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Li Chen, MS; Statistician

PrECOG

Phone: 857-284-3670

Email: Li Chen <[email protected]>

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm A n=90 participants at risk Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 participants at risk Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Gastrointestinal disorders Abdominal pain	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Appendicitis	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Cardiac disorders Atrial fibrillation	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Bacteraemia	2.2% 2/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Bacterial sepsis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Cardiac disorders Cardiac failure	2.2% 2/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Cellulitis	1.1% 1/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Colitis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Psychiatric disorders Confusional state	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Hepatobiliary disorders Drug-induced liver injury	2.2% 2/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Cardiac disorders Left ventricular dysfunction	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Cardiac disorders Myocarditis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Neutropenic colitis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Oesophagitis	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Platelet count decreased	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	4.6% 4/87 • Number of events 4 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Pneumonia	1.1% 1/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	2.3% 2/87 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Pneumonia fungal	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
General disorders Pyrexia	3.3% 3/90 • Number of events 3 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 2/90 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	2.3% 2/87 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Sepsis	11.1% 10/90 • Number of events 10 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	2.3% 2/87 • Number of events 3 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Septic shock	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Sinusitis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Sinusitis fungal	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Stomatitis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	2.3% 2/87 • Number of events 2 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Stomatitis haemorrhagic	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Streptococcal sepsis	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Thrombophlebitis septic	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Troponin I increased	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Anal fissure	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Musculoskeletal and connective tissue disorders Chondrocalcinosis	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Clostridium difficile colitis	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Psychiatric disorders Completed suicide	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations COVID-19	1.1% 1/90 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Nervous system disorders Cranial nerve disorder	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	1.1% 1/87 • Number of events 1 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.

Other adverse events
Measure	Arm A n=90 participants at risk Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Gilteritinib: Induction: 120 mg orally daily x 14 days starting on day 8 Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles	Arm B n=87 participants at risk Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Midostaurin: Induction: 50 mg orally twice daily x 14 days beginning on day 8 Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles) Daunorubicin: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3 Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3 Cytarabine: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1 Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
Investigations Alanine aminotransferase increased	17.8% 16/90 • Number of events 28 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	20.7% 18/87 • Number of events 36 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Blood and lymphatic system disorders Anaemia	31.1% 28/90 • Number of events 158 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	39.1% 34/87 • Number of events 168 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Aspartate aminotransferase increased	18.9% 17/90 • Number of events 24 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	27.6% 24/87 • Number of events 28 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Colitis	7.8% 7/90 • Number of events 8 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	5.7% 5/87 • Number of events 5 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Constipation	24.4% 22/90 • Number of events 23 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	10.3% 9/87 • Number of events 13 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Metabolism and nutrition disorders Decreased appetite	16.7% 15/90 • Number of events 22 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	13.8% 12/87 • Number of events 13 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Diarrhoea	40.0% 36/90 • Number of events 44 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	28.7% 25/87 • Number of events 34 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 15/90 • Number of events 19 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	9.2% 8/87 • Number of events 9 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
General disorders Fatigue	20.0% 18/90 • Number of events 23 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	19.5% 17/87 • Number of events 20 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Blood and lymphatic system disorders Febrile neutropenia	53.3% 48/90 • Number of events 65 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	49.4% 43/87 • Number of events 58 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Metabolism and nutrition disorders Hypocalcaemia	17.8% 16/90 • Number of events 29 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	8.0% 7/87 • Number of events 11 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Metabolism and nutrition disorders Hypokalaemia	20.0% 18/90 • Number of events 33 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	32.2% 28/87 • Number of events 61 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Lymphocyte count decreased	26.7% 24/90 • Number of events 179 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	29.9% 26/87 • Number of events 262 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Nausea	22.2% 20/90 • Number of events 27 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	25.3% 22/87 • Number of events 34 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Neutrophil count decreased	31.1% 28/90 • Number of events 92 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	39.1% 34/87 • Number of events 151 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Platelet count decreased	42.2% 38/90 • Number of events 292 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	37.9% 33/87 • Number of events 267 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
General disorders Pyrexia	17.8% 16/90 • Number of events 32 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	17.2% 15/87 • Number of events 31 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Sepsis	5.6% 5/90 • Number of events 5 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	10.3% 9/87 • Number of events 9 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Stomatitis	32.2% 29/90 • Number of events 33 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	28.7% 25/87 • Number of events 34 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Vomiting	12.2% 11/90 • Number of events 13 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	10.3% 9/87 • Number of events 11 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations White blood cell count decreased	34.4% 31/90 • Number of events 155 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	42.5% 37/87 • Number of events 225 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Abdominal pain	13.3% 12/90 • Number of events 14 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	12.6% 11/87 • Number of events 11 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Psychiatric disorders Anxiety	7.8% 7/90 • Number of events 7 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Musculoskeletal and connective tissue disorders Back pain	6.7% 6/90 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Infections and infestations Bacteraemia	8.9% 8/90 • Number of events 10 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Blood alkaline phosphatase increased	6.7% 6/90 • Number of events 7 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	8.0% 7/87 • Number of events 15 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Blood bilirubin increased	5.6% 5/90 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 8 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
General disorders Chills	10.0% 9/90 • Number of events 9 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	5.7% 5/87 • Number of events 5 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Respiratory, thoracic and mediastinal disorders Cough	7.8% 7/90 • Number of events 7 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Nervous system disorders Dizziness	13.3% 12/90 • Number of events 12 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 9 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Dry mouth	6.7% 6/90 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Nervous system disorders Dysgeusia	6.7% 6/90 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	5.7% 5/87 • Number of events 5 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.8% 7/90 • Number of events 12 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 10 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Investigations Electrocardiogram QT prolonged	6.7% 6/90 • Number of events 8 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Flatulence	5.6% 5/90 • Number of events 5 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Renal and urinary disorders Haematuria	0.00% 0/90 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	6.9% 6/87 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Nervous system disorders Headache	13.3% 12/90 • Number of events 15 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	11.5% 10/87 • Number of events 14 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.
Metabolism and nutrition disorders Hyperphosphataemia	5.6% 5/90 • Number of events 6 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.	0.00% 0/87 • Adverse events (AEs) are monitored during the 9 month treatment period for each patient, and for 30 days post-final dose, until resolution to ≤ grade 1 or stabilization, for a total of 10 months. A serious adverse event (SAE) is any untoward medical occurrence after study treatment initiation that results in death, is life-threatening, requires or prolongs hospitalization, causes disability/incapacity, is a congenital anomaly, or, based on medical judgment, may jeopardize the patient or require intervention to prevent serious outcomes.