Trial Outcomes & Findings for A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib (NCT NCT03755518)

NCT ID: NCT03755518

Last Updated: 2024-12-12

Results Overview

Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 38 participants
• Primary outcome timeframe: From First Dose to end of Cycle 6 (approximately 168 days)
• Results posted on: 2024-12-12

Participant Flow

Participant milestones

Measure	Fedratimib 400 mg/day PO (4 x 100 mg capsules)
Overall Study STARTED	38
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	38

Reasons for withdrawal

Measure	Fedratimib 400 mg/day PO (4 x 100 mg capsules)
Overall Study Lack of Efficacy	10
Overall Study Adverse Event	7
Overall Study Study Terminated by Sponsor	5
Overall Study Death	1
Overall Study Withdrawal by Subject	3
Overall Study Progressive Disease	4
Overall Study Bone Marrow Transplant	4
Overall Study Physicians Decision	1
Overall Study Relapse	1
Overall Study Withdrawal by Investigator for Non Compliance	1
Overall Study Withdrawal by PI	1

Baseline Characteristics

A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

Baseline characteristics by cohort

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Age, Continuous	68.4 Years STANDARD_DEVIATION 7.69 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
EE Population	35 Participants n=5 Participants
MFSAF Population	36 Participants n=5 Participants
Palpation evaluable population	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: From First Dose to end of Cycle 6 (approximately 168 days)

Population: Efficacy evaluable population

Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=35 Participants 400 mg/day PO (4 x 100 mg capsules)
Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6	25.7 Percentage of participants Interval 12.5 to 43.3

SECONDARY outcome

Timeframe: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 128 weeks)

Population: Safety Population

Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs All grade	38 Participants
Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs Grade 3/4	30 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)

Population: Safety Population

Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs All grade	34 Participants
Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs Grade 3/4	13 Participants

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in hematology laboratory analysis - hemoglobin

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin cycle 4 day 1	-1.16 g/dL Standard Deviation 1.431
Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin cycle 7 day 1	-1.13 g/dL Standard Deviation 1.127

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in hematology laboratory analysis - erythrocytes.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes cycle 4 day 1	-0.60 10¹²Cells/L Standard Deviation 0.567
Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes cycle 7 day 1	-0.67 10¹²Cells/L Standard Deviation 0.609

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils Baseline Platelets	0 10⁹Cells/L Standard Deviation 0
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 4 day 1 - platelets	13.8 10⁹Cells/L Standard Deviation 135.86
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 7 day 1 - platelets	11.7 10⁹Cells/L Standard Deviation 131.25
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 4 day 1 - leukocytes	-15.481 10⁹Cells/L Standard Deviation 21.6350
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 7 day 1 - leukocytes	-15.127 10⁹Cells/L Standard Deviation 18.5744
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 4 day 1 - neutrophils	-10.064 10⁹Cells/L Standard Deviation 14.2661
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils cycle 7 day 1 - neutrophils	-10.495 10⁹Cells/L Standard Deviation 13.5489

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in hematology laboratory analysis - blasts/leukocytes

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=31 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis cycle 7 day 1	-0.2 Percentage of blasts/leukocytes Standard Deviation 1.82
Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis cycle 4 day 1	0.0 Percentage of blasts/leukocytes Standard Deviation 1.50

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 4 day 1 - ALT	0.7 U/L Standard Deviation 18.49
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 7 day 1 - ALT	7.3 U/L Standard Deviation 29.53
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 4 day 1 - AST	-0.9 U/L Standard Deviation 8.71
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 7 day 1 - AST	2.3 U/L Standard Deviation 11.83
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 4 day 1 - Amylase	15.1 U/L Standard Deviation 17.17
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 7 day 1 - Amylase	10.5 U/L Standard Deviation 15.19
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 4 day 1 - Lipase	11.6 U/L Standard Deviation 19.22
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase cycle 7 day 1 - Lipase	6.4 U/L Standard Deviation 13.60

SECONDARY outcome

Timeframe: at Cycle 4 Day 1 and Cycle 7 Day 1

Population: all treated participants with both baseline and post-baseline measurements

Mean change from baseline in chemistry parameters analysis - Creatinine.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine cycle 4 day 1 - Creatinine	23.9 umol/L Standard Deviation 18.82
Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine cycle 7 day 1 - Creatinine	28.5 umol/L Standard Deviation 23.03

SECONDARY outcome

Timeframe: From First Dose to end of Cycle 6 (approximately 168 days)

Population: Palpation evaluable population

Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.

Outcome measures

Measure	Fedratimib n=37 Participants 400 mg/day PO (4 x 100 mg capsules)
Spleen Response Rate by Palpation	16.2 Percentage of Participants Interval 6.2 to 32.0

SECONDARY outcome

Timeframe: From First Dose to end of Cycle 6 (approximately 168 days)

Population: MFSAF Population

Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS > 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.

Outcome measures

Measure	Fedratimib n=36 Participants 400 mg/day PO (4 x 100 mg capsules)
Symptom Response Rate	44.4 Percentage of participants Interval 27.9 to 61.9

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.40 Weeks)

Population: EE population, Responders only

Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction < 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.

Outcome measures

Measure	Fedratimib n=24 Participants 400 mg/day PO (4 x 100 mg capsules)
Durability of Spleen Volume Response by MRI/CT (DR)	115.1 Weeks Interval 38.1 to ULN not reached. 15 participants were censored. Insufficient number of events (subsequent progressive disease or deaths) occurred to calculate the ULN via the K-M method.

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.32 Weeks)

Population: Palpation Evaluable Population, responders only

Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.

Outcome measures

Measure	Fedratimib n=21 Participants 400 mg/day PO (4 x 100 mg capsules)
Durability of Spleen Response by Palpation (DRP)	134.9 Weeks Interval 33.3 to ULN not reached. 14 participants were censored. Insufficient number of events (subsequent progressive disease or deaths) occurred to calculate the ULN via the K-M method.

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 31.33 Weeks)

Population: MFSAF population, Responders only

Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction < 50%. In the absence of TSS reduction < 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

Outcome measures

Measure	Fedratimib n=28 Participants 400 mg/day PO (4 x 100 mg capsules)
Durability of Symptom Response (DSR)	20.1 Weeks Interval 11.0 to 48.0

SECONDARY outcome

Timeframe: From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)

Population: Safety Population

Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's. Nausea	0 Participants
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's. Vomitting	0 Participants
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's. Diarrhea	0 Participants
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's. Encephalopathy	0 Participants
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's. Wernickes Encephalopathy	0 Participants

SECONDARY outcome

Timeframe: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)

Population: Safety Population

Number of participants with thiamine levels < LLN.

LLN of thiamine is 70 nmol/L.

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 1	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 2	2 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 3	2 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 6	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 9	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 12	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 15	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 18	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 21	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 24	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 42	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 45	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 48	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 51	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). cycle 54	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). End of Treatment	1 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Total number of participants with thiamine <LLN	5 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 27	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 30	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 33	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 36	0 Participants
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN). Cycle 39	0 Participants

SECONDARY outcome

Timeframe: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)

Population: Safety Population

Number of participants with thiamine levels > ULN.

ULN of thiamine is 180 nmol/L.

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 1	21 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 2	9 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 3	9 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 6	6 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 9	5 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 12	4 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 15	7 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 21	4 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 24	3 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 27	2 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 30	2 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 33	2 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 36	0 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 39	2 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 42	1 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 45	1 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 48	3 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 18	4 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 51	1 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Cycle 54	0 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). End of Treatment	9 Participants
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN). Total number of participants with thiamine > ULN	28 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)

Population: Safety Population

Number of participants with clinically notable laboratory results, Grade 3 or 4

Outcome measures

Measure	Fedratimib n=38 Participants 400 mg/day PO (4 x 100 mg capsules)
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 GFR from Creatinine adjusted for BSA (mL/min/1.73m²)	7 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Gamma Glytamyl Transferase (U/L)	2 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Lipase (U/L)	2 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Potassium (mmol/L)	1 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Sodium (mmol/L)	4 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Triglycerides (mmol/L)	1 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Hemoglobin (g/dL)	20 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Leukocytes (10⁹/L)	5 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Lymphocytes (10⁹/L)	7 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Neutrophils, Segmented (10⁹/L)	4 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Neutrophils, Segmented and Band Form (10⁹/L)	2 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Platelets (10⁹/L)	10 Participants
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4 Prothrombin INR (ratio)	1 Participants

Adverse Events

Fedratinib

Serious events: 22 serious events

Other events: 38 other events

Deaths: 16 deaths

Serious adverse events

Measure	Fedratinib n=38 participants at risk 400 mg/day PO (4 x 100 mg capsules)
Blood and lymphatic system disorders Anaemia	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Neutropenia	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Splenomegaly	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Atrial fibrillation	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Atrioventricular block complete	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Cardiac failure congestive	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Cardiac tamponade	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Myocardial ischaemia	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Pericardial effusion	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal pain upper	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Anal haemorrhage	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Ascites	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Gastric haemorrhage	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Hepatobiliary disorders Hepatic failure	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Pneumonia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Injury, poisoning and procedural complications Humerus fracture	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Blood creatinine increased	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyperkalaemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyponatraemia	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Back pain	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Muscular weakness	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma of the skin	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Cerebrovascular accident	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Haemorrhage intracranial	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Renal and urinary disorders Acute kidney injury	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Renal and urinary disorders Chronic kidney disease	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Vascular disorders Hypotension	2.6% 1/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.

Other adverse events

Measure	Fedratinib n=38 participants at risk 400 mg/day PO (4 x 100 mg capsules)
Blood and lymphatic system disorders Anaemia	60.5% 23/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Febrile neutropenia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Leukocytosis	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Leukopenia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Lymphopenia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Neutropenia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Blood and lymphatic system disorders Thrombocytopenia	39.5% 15/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Atrial fibrillation	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Sinus tachycardia	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Cardiac disorders Tachycardia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Eye disorders Lacrimation increased	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Eye disorders Vision blurred	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal hernia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal pain	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal pain lower	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Abdominal pain upper	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Ascites	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Constipation	50.0% 19/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Diarrhoea	44.7% 17/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Dry mouth	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Dyspepsia	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Melaena	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Nausea	42.1% 16/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Stomatitis	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Toothache	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Gastrointestinal disorders Vomiting	23.7% 9/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Chills	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Early satiety	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Fatigue	31.6% 12/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Influenza like illness	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Oedema peripheral	26.3% 10/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Pain	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Peripheral swelling	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
General disorders Pyrexia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Bacteraemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations COVID-19	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Candida infection	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Conjunctivitis	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Gastroenteritis viral	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Pneumonia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Infections and infestations Upper respiratory tract infection	13.2% 5/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Injury, poisoning and procedural complications Contusion	18.4% 7/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Injury, poisoning and procedural complications Fall	13.2% 5/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Injury, poisoning and procedural complications Skin laceration	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Alanine aminotransferase increased	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Amylase increased	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Aspartate aminotransferase increased	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Blast cell count increased	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Blood alkaline phosphatase increased	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Blood creatinine increased	36.8% 14/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Glomerular filtration rate decreased	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Lipase increased	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Vitamin B1 decreased	18.4% 7/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Investigations Weight decreased	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Decreased appetite	23.7% 9/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Gout	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyperglycaemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyperkalaemia	15.8% 6/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyperphosphataemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyperuricaemia	18.4% 7/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hypocalcaemia	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hypoglycaemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hypokalaemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hypomagnesaemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hyponatraemia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Metabolism and nutrition disorders Hypophosphataemia	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Arthralgia	18.4% 7/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Back pain	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Bone pain	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Muscle spasms	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Muscular weakness	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Musculoskeletal and connective tissue disorders Pain in extremity	15.8% 6/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Disturbance in attention	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Dizziness	26.3% 10/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Encephalopathy	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Headache	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Hypoaesthesia	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Neuropathy peripheral	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Paraesthesia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Peripheral sensory neuropathy	15.8% 6/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Nervous system disorders Tremor	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Psychiatric disorders Anxiety	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Psychiatric disorders Depression	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Psychiatric disorders Insomnia	23.7% 9/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Renal and urinary disorders Acute kidney injury	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Renal and urinary disorders Dysuria	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Renal and urinary disorders Pollakiuria	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Cough	26.3% 10/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	31.6% 12/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.2% 5/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Alopecia	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Dry skin	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Erythema	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Night sweats	7.9% 3/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Onychoclasis	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Pruritus	26.3% 10/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Purpura	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Rash	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Skin and subcutaneous tissue disorders Skin exfoliation	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Vascular disorders Hot flush	5.3% 2/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.
Vascular disorders Hypertension	10.5% 4/38 • Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All-Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 56 Months. Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: 1-855-907-3286

Email: Clinical.Trials@bms.com

Results disclosure agreements

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

Restriction type: LTE60