Phase 2 Study: An Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post- Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib

• Sponsor: CTI BioPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04884191
• Collaborator: (none)
• Enrollment: 165
• Locations: 62
• Arms: 3
• Actual Duration (Months): 25.1
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open-label, randomized, dose-finding study in patients with primary or secondary MF (Dynamic International Prognostic Scoring System [DIPSS] risk score of Intermediate-1 to High-Risk) who were previously treated with ruxolitinib. The study was designed to support a pacritinib dosage selection decision with evaluation of 3 dosages.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post- Essential Thrombocythemia Myelofibrosis	Drug: Pacritinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study: An Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post- Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib
• Actual Study Start Date: Jul 31, 2017
• Actual Primary Completion Date: Sep 4, 2019
• Actual Study Completion Date: Sep 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pacritinib 100 mg QD	Drug: Pacritinib; Pacritinib
Experimental: Pacritinib 100 mg BID	Drug: Pacritinib; Pacritinib
Experimental: Pacritinib 200 mg BID	Drug: Pacritinib; Pacritinib

Outcome Measures

Primary Outcome Measures

1. Spleen Volume Reduction Response (≥ 35%) [From Baseline to Weeks 12 and 24]

   Number of patients achieving a ≥ 35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans

2. Percent Change in Spleen Volume [From Baseline to Weeks 12 and 24]

   Percent change from baseline

3. Total Symptom Score Analysis [From Baseline to Weeks 12 and 24]

   Proportion of patients with ≥ 50% reduction in Total Symptom Score from baseline as assessed by the validated PRO instrument MPN-SAF TSS 2.0

4. Patient Global Impression Assessment [From Baseline to Weeks 12 and 24]

   Number of patients with improvement in PGIA. The Patient Global Impression Assessment questionnaire was completed at the end of Week 12 and end of Week 24. The scores were summarized by treatment group at each visit.

Secondary Outcome Measures

1. Spleen Length Reduction [From Baseline to Weeks 24]

   Rate of reduction in spleen length from baseline

2. Frequency of RBC's or Platelet Transfusions [At week 24]

   Number of patients

3. Eastern Cooperative Oncology Group Performance Status [At weeks 4, 12, 24, and 30 days post End-of-Treatment visit]

   0 = Fully active, able to carry on all pre-disease performance without restriction = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair = Dead

4. Number of Participants With Adverse Events [Randomization through 30 days post End-of-Treatment visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)

2. DIPSS Intermediate-1, Intermediate -2, or High-risk (Passamonti et al 2010)

3. Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following:

4. Treatment for ≥3 months with inadequate efficacy response defined as <10% SVR by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response; and/or

5. Treatment for ≥28 days complicated by either

1. Development of a red blood cell (RBC) transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (NCI) CTCAE grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of <20 mg BID

1. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination

2. TSS of ≥10 on the MPN-SAF TSS 2.0 or patients with a single symptom score of ≥5 or 2 symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats

3. Age ≥18 years old

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

5. Peripheral blast count of <10% throughout the Screening period

6. Absolute neutrophil count of >500/μL

7. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase [SGPT]), ≤3 × the upper limit of normal (ULN) (AST/ALT ≤5 × ULN, if transaminase elevation is related to MF), direct bilirubin ≤4× ULN, and creatinine ≤2.5 mg/dL

8. Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN

9. Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan

10. If fertile, willing to use effective birth control methods during the study

11. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study

12. Able to understand and willing to complete symptom assessments using a PRO instrument

13. Provision of informed consent

Exclusion Criteria:

1. Life expectancy <6 months

2. Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete allo-SCT

3. History of splenectomy or planning to undergo splenectomy

4. Splenic irradiation within the last 6 months

5. Previously treated with pacritinib

6. Patients receiving high-dose ruxolitinib (more than 10 mg BID or 20 mg QD) who cannot tolerate tapering down ruxolitinib to 10 mg BID or less prior to the first dose of pacritinib

7. Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ≤100 mg per day, within the last 2 weeks

8. Treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 inducer within the last 2 weeks

9. Treatment with medications that can prolong the QTc interval within the last 2 weeks

10. Treatment with an experimental therapy within the last 28 days

11. Significant recent bleeding history defined as NCI CTCAE grade ≥2 within the last 3 months, unless precipitated by an inciting event (eg, surgery, trauma, or injury)

12. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety.

13. New York Heart Association Class II, III, or IV congestive heart failure

14. Any history of CTCAE grade ≥2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the medical monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.

15. QTc prolongation >450 ms based on the mean of triplicate ECGs or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)

16. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication

17. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or constipation

18. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma

19. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection or psychiatric illness or social situation that, in the judgment of the treating physician, would limit compliance with study requirements

20. Known seropositivity for human immunodeficiency virus

21. Known active hepatitis A, B, or C virus infection

22. Women who are pregnant or lactating

23. Concurrent enrollment in another interventional trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	City of Hope	Duarte	California	United States	91010
3	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
5	Stanford Cancer Institute	Stanford	California	United States	94305
6	Yale School of Medicine	New Haven	Connecticut	United States	06520
7	Medical Faculty Associates, Inc.	Washington	District of Columbia	United States	20037
8	Florida Cancer Specialists & Research Institute	Fort Myers	Florida	United States	33901
9	Florida Cancer Specialists & Research Institute	Saint Petersburg	Florida	United States	33705
10	Florida Cancer Specialists & Research Institute	West Palm Beach	Florida	United States	33401
11	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
12	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
13	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
14	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
15	Saint Agnes Hospital	Baltimore	Maryland	United States	21229
16	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
17	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
18	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
19	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
20	Weill Cornell Medical College	New York	New York	United States	10021
21	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
22	Columbia University	New York	New York	United States	10032
23	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
24	University of Rochester	Rochester	New York	United States	14642
25	Duke University Hospital	Durham	North Carolina	United States	27710
26	Cleveland Clinic	Cleveland	Ohio	United States	44195
27	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
28	Tennessee Oncology	Nashville	Tennessee	United States	37203
29	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
30	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
31	University of Texas Health Science Center at San Antonio School of Medicine	San Antonio	Texas	United States	78229
32	University of Utah School of Medicine	Salt Lake City	Utah	United States	84112
33	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
34	CHU Hopital Sud	Amiens		France	80054
35	Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez	Lille Cedex		France	59037
36	CHU de Nimes - Hopital Universitaire Caremeau	Nîmes		France	30029
37	Hôpital Saint-Louis	Paris		France	75010
38	CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque	Pessac		France	33604
39	Centre Hospitalier Lyon-Sud	Pierre-Bénite		France	69495
40	Centre Hospitalier Universitaire de Toulouse- Hôpital Purpan	Toulouse Cedex		France	31059
41	SE AOK I. sx. Belgyogyaszati Klinika	Budapest		Hungary	1083
42	Debreceni Egyetem Klinikai Központ	Debrecen		Hungary	4032
43	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár		Hungary	7400
44	Azienda Ospedaliero-Universitaria Careggi	Firenze		Italy	50134
45	Istituto Scientifico Romagnolo per lo Studio e la Cura Dei Tumori	Meldola		Italy	47014
46	ASST Monza - Ospedale San Gerardo	Monza		Italy	20900
47	Yeungnam University Medical Center	Daegu		Korea, Republic of	42415
48	Severance Hospital	Seoul		Korea, Republic of	03722
49	Samsung Medical Center	Seoul		Korea, Republic of	06351
50	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
51	Hospital del Mar	Barcelona		Spain	08003
52	Hospital Clínic de Barcelona	Barcelona		Spain	08036
53	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
54	Clínica Universidad de Navarra	Pamplona		Spain	31008
55	Skane University Hospital Lund	Lund		Sweden	22185
56	Orebro University Hospital	Örebro		Sweden	70185
57	Beatson West of Scotland Cancer Center	Glasgow		United Kingdom	G12 0YN
58	Barts Health NHS Trust - The Royal London Hospital	London		United Kingdom	E1 2ES
59	Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital	London		United Kingdom	SE1 9RT
60	Imperial College Healthcare NHS Trust - Hammersmith Hospital	London		United Kingdom	W12 0HS
61	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
62	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford		United Kingdom	OX3 7LE

Sponsors and Collaborators

• CTI BioPharma

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 6, 2019
• Statistical Analysis Plan - Nov 1, 2019

More Information

Publications

None provided.

• Responsible Party: CTI BioPharma
• ClinicalTrials.gov Identifier: NCT04884191
• Other Study ID Numbers: PAC203
• First Posted: May 12, 2021
• Last Update Posted: Jun 1, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential

Study Results

Participant Flow

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Period Title: Overall Study
STARTED	55	55	55
COMPLETED	52	55	54
NOT COMPLETED	3	0	1

Baseline Characteristics

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID	Total
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Total of all reporting groups
Overall Participants	52	55	54	161
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	16 30.8%	11 20%	16 29.6%	43 26.7%
>=65 years	36 69.2%	44 80%	38 70.4%	118 73.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (8.8)	68.9 (6.9)	68.1 (8.76)	68.7 (8.14)
Sex: Female, Male (Count of Participants)
Female	21 40.4%	26 47.3%	22 40.7%	69 42.9%
Male	31 59.6%	29 52.7%	32 59.3%	92 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 1.9%	1 0.6%
Asian	2 3.8%	1 1.8%	1 1.9%	4 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 1.9%	0 0%	4 7.4%	5 3.1%
White	44 84.6%	47 85.5%	48 88.9%	139 86.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 9.6%	7 12.7%	0 0%	12 7.5%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.1 (3.79)	27.2 (4.11)	26.4 (5)	26.3 (4.4)
ECOG PS (participants) [Number]
0	11 21.2%	14 25.5%	17 31.5%	42 26.1%
1	32 61.5%	29 52.7%	29 53.7%	90 55.9%
2	9 17.3%	12 21.8%	8 14.8%	29 18%

Outcome Measures

1. Primary Outcome

Title	Spleen Volume Reduction Response (≥ 35%)
Description	Number of patients achieving a ≥ 35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans
Time Frame	From Baseline to Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	52	55	54
End of Week 12	0 0%	2 3.6%	2 3.7%
End of Week 24	0 0%	1 1.8%	5 9.3%

2. Primary Outcome

Title	Percent Change in Spleen Volume
Description	Percent change from baseline
Time Frame	From Baseline to Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

The difference between the number of participants analyzed in Week 12 vs. Week 24 is the result of the number of participants that continued to complete the study. Participants that were not analyzed were withdrawn from the study for various reasons.

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	38	43	43
Week 12	3.19 (22.613)	6.37 (31.110)	-3.60 (26.610)
Week 24	-2.43 (17.608)	0.65 (20.589)	-11.30 (26.417)

3. Primary Outcome

Title	Total Symptom Score Analysis
Description	Proportion of patients with ≥ 50% reduction in Total Symptom Score from baseline as assessed by the validated PRO instrument MPN-SAF TSS 2.0
Time Frame	From Baseline to Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	52	55	54
End of Week 12	1 1.9%	1 1.8%	2 3.7%
End of Week 24	2 3.8%	0 0%	2 3.7%

4. Primary Outcome

Title	Patient Global Impression Assessment
Description	Number of patients with improvement in PGIA. The Patient Global Impression Assessment questionnaire was completed at the end of Week 12 and end of Week 24. The scores were summarized by treatment group at each visit.
Time Frame	From Baseline to Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	52	55	54
Week 12 - Any Improved	17 32.7%	21 38.2%	23 42.6%
Week 12 -No Change	6 11.5%	5 9.1%	8 14.8%
Week 12 -Any Worse	8 15.4%	8 14.5%	3 5.6%
Week 24 - Any Improved	10 19.2%	13 23.6%	18 33.3%
Week 24 -No Change	6 11.5%	5 9.1%	1 1.9%
Week 24 -Any Worse	5 9.6%	3 5.5%	2 3.7%

5. Secondary Outcome

Title	Spleen Length Reduction
Description	Rate of reduction in spleen length from baseline
Time Frame	From Baseline to Weeks 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	24	25	27
Mean (Standard Deviation) [cm]	12.42 (5.602)	11.48 (6.501)	11.63 (7.131)

6. Secondary Outcome

Title	Frequency of RBC's or Platelet Transfusions
Description	Number of patients
Time Frame	At week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	20	20	20
Mean (Standard Deviation) [transfusions/month]	2.27 (2.987)	1.18 (2.553)	2.25 (2.345)

7. Secondary Outcome

Title	Eastern Cooperative Oncology Group Performance Status
Description	0 = Fully active, able to carry on all pre-disease performance without restriction = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair = Dead
Time Frame	At weeks 4, 12, 24, and 30 days post End-of-Treatment visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	52	55	54
Week 4 - 0	10 19.2%	11 20%	13 24.1%
Week 4 - 1	28 53.8%	27 49.1%	31 57.4%
Week 4 - 2	9 17.3%	16 29.1%	8 14.8%
Week 4 - 3	2 3.8%	0 0%	0 0%
Week 4 - 4	0 0%	0 0%	0 0%
Week 4 - 5	0 0%	0 0%	0 0%
Week 12 - 0	11 21.2%	9 16.4%	14 25.9%
Week 12 - 1	20 38.5%	23 41.8%	19 35.2%
Week 12 - 2	8 15.4%	10 18.2%	8 14.8%
Week 12 - 3	1 1.9%	1 1.8%	2 3.7%
Week 12 - 4	0 0%	0 0%	0 0%
Week 12 - 5	0 0%	0 0%	0 0%
Week 24 - 0	10 19.2%	6 10.9%	10 18.5%
Week 24 - 1	12 23.1%	15 27.3%	12 22.2%
Week 24 - 2	4 7.7%	5 9.1%	6 11.1%
Week 24 - 3	0 0%	0 0%	0 0%
Week 24 - 4	0 0%	0 0%	0 0%
Week 24 - 5	0 0%	0 0%	0 0%
End of Treatment - 0	11 21.2%	8 14.5%	8 14.8%
End of Treatment - 1	19 36.5%	23 41.8%	22 40.7%
End of Treatment - 2	5 9.6%	10 18.2%	11 20.4%
End of Treatment - 3	1 1.9%	1 1.8%	2 3.7%
End of Treatment - 4	0 0%	0 0%	0 0%
End of Treatment - 5	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Time Frame	Randomization through 30 days post End-of-Treatment visit

Outcome Measure Data

Analysis Population Description

Patients with ≥ 1 TEAE

Arm/Group Title	Pacritinib 100 mg QD	Pacritinib 100 mg BID	Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib	Pacritinib: Pacritinib	Pacritinib: Pacritinib
Measure Participants	52	55	54
Count of Participants [Participants]	49 94.2%	51 92.7%	54 100%

Adverse Events

Time Frame	The end of assigned study drug + 30 days
Adverse Event Reporting Description	AEs analyzed in the Safety Population
Arm/Group Title	Pacritinib 100 mg QD		Pacritinib 100 mg BID		Pacritinib 200 mg BID
Arm/Group Description	Pacritinib: Pacritinib		Pacritinib: Pacritinib		Pacritinib: Pacritinib
All Cause Mortality
	Pacritinib 100 mg QD		Pacritinib 100 mg BID		Pacritinib 200 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/52 (11.5%)		4/55 (7.3%)		5/54 (9.3%)
Serious Adverse Events
	Pacritinib 100 mg QD		Pacritinib 100 mg BID		Pacritinib 200 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/52 (36.5%)		20/55 (36.4%)		25/54 (46.3%)
Blood and lymphatic system disorders
Anaemia	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Febrile neutropenia	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Lymphadenopathy	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Splenic infarction	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Thrombocytopenia	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Thrombocytosis	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Cardiac disorders
Pericardial effusion	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Arrhythmia supraventricular	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Atrial fibrillation	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Cardiac failure	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Gastrointestinal disorders
Colitis	1/52 (1.9%)		1/55 (1.8%)		0/54 (0%)
Large intestinal obstruction	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Ascites	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Diarrhoea	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Gastrointestinal haemorrhage	0/52 (0%)		0/55 (0%)		2/54 (3.7%)
Intestinal obstruction	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
General disorders
Pyrexia	3/52 (5.8%)		2/55 (3.6%)		3/54 (5.6%)
General physical health deterioration	2/52 (3.8%)		0/55 (0%)		0/54 (0%)
Disease progression	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Drug withdrawal syndrome	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Oedema peripheral	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Asthenia	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Non-cardiac chest pain	0/52 (0%)		2/55 (3.6%)		0/54 (0%)
Infections and infestations
Pneumonia	2/52 (3.8%)		2/55 (3.6%)		5/54 (9.3%)
Cellulitis	1/52 (1.9%)		1/55 (1.8%)		0/54 (0%)
Diverticulitis	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Post procedural infection	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Pyelonephritis	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Sepsis	1/52 (1.9%)		1/55 (1.8%)		2/54 (3.7%)
Tuberculosis	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Urinary tract infection	1/52 (1.9%)		2/55 (3.6%)		1/54 (1.9%)
Abscess limb	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Bronchitis	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Clostridium difficile colitis	0/52 (0%)		1/55 (1.8%)		2/54 (3.7%)
Gastroenteritis	0/52 (0%)		1/55 (1.8%)		2/54 (3.7%)
Herpes oesophagitis	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Influenza	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Lower respiratory tract infection	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Soft tissue infection	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Tooth abscess	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	1/52 (1.9%)		0/55 (0%)		1/54 (1.9%)
Transfusion reaction	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Delayed haemolytic transfusion reaction	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Incorrect drug administration duration	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Subdural haemorrhage	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Investigations
Blood bilirubin increased	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Ejection fraction decreased	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Troponin increased	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Metabolism and nutrition disorders
Hyperuricaemia	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Dehydration	0/52 (0%)		3/55 (5.5%)		2/54 (3.7%)
Fluid overload	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Hypokalaemia	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Musculoskeletal and connective tissue disorders
Bone pain	1/52 (1.9%)		0/55 (0%)		1/54 (1.9%)
Muscle haemorrhage	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Malignant pleural effusion	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Myeloproliferative disorder	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Pituitary tumour benign	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Prostate cancer	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Nervous system disorders
Optic neuritis	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Syncope	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Headache	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Renal and urinary disorders
Haematuria	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Renal failure acute	1/52 (1.9%)		0/55 (0%)		2/54 (3.7%)
Calculus ureteric	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Hydronephrosis	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Renal impairment	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Renal mass	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/52 (3.8%)		0/55 (0%)		0/54 (0%)
Dyspnoea	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Hypoxia	0/52 (0%)		1/55 (1.8%)		1/54 (1.9%)
Respiratory distress	0/52 (0%)		0/55 (0%)		0/54 (0%)
Respiratory failure	0/52 (0%)		0/55 (0%)		1/54 (1.9%)
Skin and subcutaneous tissue disorders
Lung infiltration	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Vascular disorders
Haematoma	1/52 (1.9%)		0/55 (0%)		1/54 (1.9%)
Vascular compression	1/52 (1.9%)		0/55 (0%)		0/54 (0%)
Hypotension	0/52 (0%)		1/55 (1.8%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Pacritinib 100 mg QD		Pacritinib 100 mg BID		Pacritinib 200 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/52 (46.2%)		34/55 (61.8%)		36/54 (66.7%)
Blood and lymphatic system disorders
Thrombocytopenia	3/52 (5.8%)		5/55 (9.1%)		9/54 (16.7%)
Anaemia	1/52 (1.9%)		3/55 (5.5%)		6/54 (11.1%)
Gastrointestinal disorders
Diarrhoea	6/52 (11.5%)		8/55 (14.5%)		14/54 (25.9%)
Nausea	7/52 (13.5%)		7/55 (12.7%)		3/54 (5.6%)
General disorders
Fatigue	1/52 (1.9%)		7/55 (12.7%)		5/54 (9.3%)
Pyrexia	1/52 (1.9%)		3/55 (5.5%)		1/54 (1.9%)
Infections and infestations
Bronchitis	3/52 (5.8%)		1/55 (1.8%)		1/54 (1.9%)
Investigations
Ejection fraction decreased	1/52 (1.9%)		3/55 (5.5%)		2/54 (3.7%)
Metabolism and nutrition disorders
Decreased appetite	3/52 (5.8%)		2/55 (3.6%)		3/54 (5.6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/52 (3.8%)		1/55 (1.8%)		3/54 (5.6%)
Dyspnoea	0/52 (0%)		3/55 (5.5%)		1/54 (1.9%)
Skin and subcutaneous tissue disorders
Pruritus	1/52 (1.9%)		3/55 (5.5%)		0/54 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.