PAC326: Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia

• Sponsor: CTI BioPharma (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02055781
• Collaborator: (none)
• Enrollment: 311
• Locations: 122
• Arms: 3
• Actual Duration (Months): 26
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with thrombocytopenia and primary or secondary myelofibrosis.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis	Drug: Pacritinib; Drug: Best Available Therapy	Phase 3

Detailed Description

Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with thrombocytopenia and primary or secondary myelofibrosis. Approximately 300 eligible patients will be randomized in a 1:1:1 allocation to pacritinib 400 mg dosed QD, pacritinib 200 mg dosed BID, or BAT (includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry). Spleen volume will be measured by MRI or CT at baseline and every 12 weeks thereafter. An independent radiology facility (IRF), blind to treatment assignments, will measure spleen volumes. Patients will also be followed for safety, Leukemia Free Survival (LFS), Overall Survival (OS), frequency of red blood cell (RBC) and platelet transfusions, and other exploratory endpoints. An Independent Data Monitoring Committee (IDMC) will evaluate the safety of pacritinib.

Study Design

• Study Type: Interventional
• Actual Enrollment: 311 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pacritinib, Once Daily Pacritinib 400 mg QD	Drug: Pacritinib
Experimental: Pacritinib, Twice Daily Pacritinib 200 mg BID	Drug: Pacritinib
Active Comparator: Best Available Therapy BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.	Drug: Best Available Therapy

Outcome Measures

Primary Outcome Measures

1. Spleen Volume Reduction [Baseline to Week 24]

   Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).

2. Total Symptom Score (TSS) Reduction [Baseline to Week 24]

   Proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 [absent] to 10 [worst imaginable]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)

• Thrombocytopenia (platelet count ≤ 100,000/µL) at any time after signing informed consent

• Palpable splenomegaly ≥ 5 cm on physical examination

• Total Symptom Score ≥ 13 on the MPN-SAF TSS 2.0, not including the inactivity question

• Patients who are platelet or red blood cell transfusion-dependent are eligible

• Adequate white blood cell counts (with low blast counts), liver function, and renal function

• At least 6 months from prior splenic irradiation

• At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent

• Not pregnant, not lactating, and agree to use effective birth control

• Able and willing to undergo frequent MRI or CT assessments and complete symptom assessments using a patient-reported outcome instrument

Exclusion Criteria:

• Prior treatment with more than 2 JAK2 inhibitors or with pacritinib

• There is no maximum cumulative prior JAK2 inhibitor treatment

• History of (or plans to undergo) spleen removal surgery or allogeneic stem cell transplant

• Ongoing gastrointestinal medical condition such as Crohn's disease, Inflammatory bowel disease, chronic diarrhea, or constipation

• Active bleeding that requires hospitalization during the screening period

• Cardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction

• Other malignancy within last 3 years other than certain limited skin, cervical, prostate, breast, or bladder cancers

• Other ongoing, uncontrolled illnesses (including HIV infection and active hepatitis A, B, or C), psychiatric disorder, or social situation that would prevent good care on this study

• Life expectancy < 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Scottsdale	Arizona	United States	85259
2	Arizona Clinical Research Center	Tucson	Arizona	United States	85715
3	City of Hope	Duarte	California	United States	91010
4	Moores Cancer Centre	La Jolla	California	United States	92093
5	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
6	Stanford Cancer Center	Stanford	California	United States	94305
7	Rocky Mountain Cancer Center	Boulder	Colorado	United States	80303
8	George Washington University- Medical Faculty Associates	Washington	District of Columbia	United States	20037
9	SCRI- Florida Cancer Specialists South Region	Fort Myers	Florida	United States	33916
10	SCRI - Florida Cancer Specialists North Region	Saint Petersburg	Florida	United States	33705
11	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
12	Northwestern University	Chicago	Illinois	United States	60611
13	Carle Cancer Center	Urbana	Illinois	United States	61801
14	Indiana University Goshen Cancer Centre	Goshen	Indiana	United States	46526
15	Investigative Clinical Research of Indiana	Indianapolis	Indiana	United States	46260
16	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
17	Siouxland Hematology-Oncology Associates, L.L.P (SHOA)	Sioux City	Iowa	United States	51101
18	Norton Cancer Institute, Suburban	Louisville	Kentucky	United States	40207
19	St Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
20	University of Michigan	Ann Arbor	Michigan	United States	48109
21	Henry Ford Health System	Detroit	Michigan	United States	48202
22	Providence Cancer Institute	Southfield	Michigan	United States	48075
23	Washington University School of Medicine Division of Oncology	Saint Louis	Missouri	United States	63110
24	Nebraska Hematology-Oncology, P.C.	Lincoln	Nebraska	United States	68506
25	Hackensack University	Hackensack	New Jersey	United States	07601
26	Hematology-Oncology Associates of Northern Jersey	Morristown	New Jersey	United States	07962
27	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87106
28	Mount Sinai Medical Center	New York	New York	United States	10029
29	Columbia University Medical Center	New York	New York	United States	10032
30	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
31	SCRI-Oncology Hematology Care	Cincinnati	Ohio	United States	45242
32	Cleveland Clinic-Taussig Cancer Center	Cleveland	Ohio	United States	44195
33	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
34	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
35	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
36	Upstate Oncology Associates	Greenville	South Carolina	United States	29601
37	Sarah Cannon Research Institute (SCRI)	Nashville	Tennessee	United States	37203
38	Texas Onocolgy-Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
39	UT Southwestern Medical Center	Dallas	Texas	United States	75390
40	UTMB Galveston	Galveston	Texas	United States	77555
41	Houston Methodist	Houston	Texas	United States	77030
42	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
43	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78229
44	Huntsman Cancer Hospital	Salt Lake City	Utah	United States	84112
45	Virginia Cancer Specialists	Leesburg	Virginia	United States	20176
46	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
47	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
48	Green Bay Oncology	Green Bay	Wisconsin	United States	54301
49	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
50	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
51	St George Hospital	Kogarah	New South Wales	Australia	2217
52	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
53	Box Hill Hospital	Box Hill	Victoria	Australia	3128
54	Monash Health - Monash Medical Centre	Clayton	Victoria	Australia	3168
55	Perth Blood Institute	Nedlands	Western Australia	Australia	6009
56	Haematology and Oncology Clinics of Australia	Chermside		Australia	4032
57	Prince of Wales Hospital	Randwick		Australia	2031
58	Centre Hospitalier de Jolimont-Lobbes	Haine-Saint-Paul	Hainaut	Belgium
59	ZNA - Stuivenberg	Antwerpen		Belgium	2060
60	AZ Sint Jan Brugge-Oostende AV	Brugge		Belgium	8000
61	Hopital Brugmann	Brussels		Belgium	1020
62	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
63	St Augustinus	Wilrijk		Belgium	2610
64	UC Louvain	Yvoir		Belgium	5530
65	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
66	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G2M9
67	Fakultní nemocnice Brno	Brno	NAP	Czechia	62500
68	Faculty Hospital Olomouc	Olomouc	NAP	Czechia	775 20
69	Fakultní nemocnice Plzeň	Plzeň	NAP	Czechia	30460
70	University Hospital Hradec Kralove	Králová		Czechia	500 05
71	Chu d'Amiens Hopital Sud	Amiens	Cedex 1	France	80054
72	Hôpital Caremeau	Nimes	Cedex 9	France	30029
73	CHU Rennes	Rennes	Cedex 9	France	35033
74	CHU Purpan	Toulouse	Cedex 9	France	31059
75	CH de Mulhouse	Mulhouse	Cedex	France	68070
76	CHU de CAEN	Caen		France	14000
77	Centre Hospitalier de Lens	Lens		France	62300
78	Hopital l'Archet, CHU de Nice	Nice		France	BP 30 79 06202
79	Saint Antoine Hospital	Paris		France	75012
80	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
81	CHU de Strasbourg	Strasbourg		France	67091
82	Institut Gustave Roussy	Villejuif Cedex		France	94805
83	Charite-Medical University	Berlin		Germany	12203
84	Gemeinschaftspraxis Hämatologie/Onkologie	Dresden		Germany	01307
85	University Hospital Essen	Essen		Germany	D-45122
86	Uniklinik Freiburg	Freiburg		Germany	79106
87	Universitatsklinikum Halle (Saale)	Halle (Saale)		Germany	06120
88	Klinik I fur Innere Medizin, Universitat Koln	Koln		Germany	50924
89	University Hospital Leipzig	Leipzig		Germany	04103
90	Städtisches Klinikum München GmbH	Munchen		Germany	81737
91	University of Munster	Munster		Germany	48149
92	University Hospital Ulm	Ulm		Germany	89081
93	Semmelweis Egyetem AOK	Budapest		Hungary	1083
94	University of Debrecen, Belgyogyaszati Intezet	Debrecen		Hungary	4032
95	Bekes Megyei Pandy Kalman Korhaz	Gyula		Hungary	5700
96	Kaposi Mór Oktató Kórház	Kaposvár		Hungary	7400
97	SZTE II. sz Belgyogyoszati Klinika es Kardiologiai Kozpont	Szeged		Hungary	6720
98	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőint	Szolnok		Hungary	5004
99	University Hospital Maastricht	Maastricht		Netherlands	6229 HX
100	Erasmus MC	Rotterdam		Netherlands	3015 CE
101	Auckland District Health Board, Auckland City Hospital	Auckland		New Zealand	1023
102	Middlemore Hospital	Auckland		New Zealand	1640
103	Canterbury District Health Board	Christchurch		New Zealand	8001
104	North Shore Hospital	Takapuna		New Zealand	0740
105	CCDHB - Wellington Hospital	Wellington		New Zealand	6021
106	Bashkir State Medical University	Ufa	Republic Of Bashkortostan	Russian Federation	450083
107	Saratov State Medical University	Saratov	Saratov Region	Russian Federation	410028
108	National Haematology Research Center	Moscow		Russian Federation	125167
109	Republican Hopsital n.a. V.A. Baranov	Petrozavodsk		Russian Federation	185019
110	Ryazan Regional Clinical Hospital	Ryazan		Russian Federation	390039
111	Russian Research Institute of Hematology and Transfusiology	St. Petersburg		Russian Federation	191024
112	Military Medical Academy n.a. S.M. Kirov	St. Petersburg		Russian Federation	194044
113	Royal Liverpool University Hospital	Liverpool	Merseyside	United Kingdom	L7 8XP
114	Belfast Health and Social Care Trust	Belfast	N. Ireland	United Kingdom	BT9 7AB
115	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
116	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 OYN
117	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
118	Guy's Hospital	London		United Kingdom	SE1 9RT
119	Hammersmith Hosp - ICH NHS Trust	London		United Kingdom	W12 OHS
120	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
121	Oxford University Hospitals NHS Trust	Oxford		United Kingdom	OX3 7LE
122	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• CTI BioPharma

Investigators

• Study Director: Simran Singh, Sr. Director, Head of Clinical Operations

Study Documents (Full-Text)

None provided.

More Information

Publications

• Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):652-659. doi: 10.1001/jamaoncol.2017.5818.

• Responsible Party: CTI BioPharma
• ClinicalTrials.gov Identifier: NCT02055781
• Other Study ID Numbers: PERSIST-2 (PAC326)
• First Posted: Feb 5, 2014
• Last Update Posted: Nov 18, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by CTI BioPharma: Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis; Primary Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Bone Marrow Disease; Hematologic Diseases; Hemorrhagic Disorders; Splenomegaly; Pacritinib; MPN-SAF; MPN-SAF TSS; Anemia; Myeloproliferative Neoplasm; Spleen volume; Thrombocytopenia; SB1518
• Additional relevant MeSH terms: Polycythemia Vera; Thrombocytopenia; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential

Study Results

Participant Flow

Arm/Group Title	Pacritinib, QD	Pacritinib, BID	Best Available Therapy
Arm/Group Description	Pacritinib 400 mg QD	Pacritinib 200 mg BID	BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Period Title: Overall Study
STARTED	104	107	100
COMPLETED	62	79	63
NOT COMPLETED	42	28	37

Baseline Characteristics

Arm/Group Title	Pacritinib, Once Daily	Pacritinib, Twice Daily	Best Available Therapy	Total
Arm/Group Description	Pacritinib 400 mg, once daily	Pacritinib 200 mg, twice daily	BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.	Total of all reporting groups
Overall Participants	104	107	100	311
Age (Count of Participants)
<=18 years	32 30.8%	41 38.3%	32 32%	105 33.8%
Between 18 and 65 years	70 67.3%	65 60.7%	68 68%	203 65.3%
>=65 years	2 1.9%	1 0.9%	0 0%	3 1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (8.55)	65.9 (8.75)	66.9 (9.75)	67.2 (9.01)
Sex: Female, Male (Count of Participants)
Female	51 49%	44 41.1%	45 45%	140 45%
Male	53 51%	63 58.9%	55 55%	171 55%
Region of Enrollment (Count of Participants)
New Zealand	4 3.8%	6 5.6%	3 3%	13 4.2%
Canada	5 4.8%	2 1.9%	4 4%	11 3.5%
Netherlands	0 0%	1 0.9%	1 1%	2 0.6%
Belgium	2 1.9%	2 1.9%	1 1%	5 1.6%
Hungary	9 8.7%	8 7.5%	7 7%	24 7.7%
United States	44 42.3%	44 41.1%	43 43%	131 42.1%
Czechia	2 1.9%	4 3.7%	5 5%	11 3.5%
United Kingdom	5 4.8%	11 10.3%	11 11%	27 8.7%
Australia	4 3.8%	5 4.7%	4 4%	13 4.2%
France	8 7.7%	10 9.3%	9 9%	27 8.7%
Germany	10 9.6%	4 3.7%	3 3%	17 5.5%
Russia	11 10.6%	10 9.3%	9 9%	30 9.6%

Outcome Measures

1. Primary Outcome

Title	Spleen Volume Reduction
Description	Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib, Once Daily	Pacritinib, Twice Daily	Best Available Therapy
Arm/Group Description	Pacritinib 400 mg, once daily	Pacritinib 200 mg, twice daily	BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Measure Participants	75	74	72
Count of Participants [Participants]	11 10.6%	16 15%	2 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Once Daily, Pacritinib, Twice Daily, Best Available Therapy
	Comments	BAT arm compared to pooled pacritinib arms (QD + BID - ITT Efficacy)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Once Daily, Best Available Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0173
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Twice Daily, Best Available Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Total Symptom Score (TSS) Reduction
Description	Proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 [absent] to 10 [worst imaginable]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pacritinib, Once Daily	Pacritinib, Twice Daily	Best Available Therapy
Arm/Group Description	Pacritinib 400 mg, once daily	Pacritinib 200 mg, twice daily	BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Measure Participants	75	74	72
Count of Participants [Participants]	13 12.5%	24 22.4%	10 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Once Daily, Pacritinib, Twice Daily, Best Available Therapy
	Comments	BAT arm compared to pooled pacritinib arms (QD + BID - ITT Efficacy)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0791
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Once Daily, Best Available Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6524
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pacritinib, Twice Daily, Best Available Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	From the time of signing informed consent through 30 days after the last study treatment.
Adverse Event Reporting Description	All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Arm/Group Title	Pacritinib, Once Daily		Pacritinib, Twice Daily		Best Available Therapy
Arm/Group Description	Pacritinib 400 mg, once daily		Pacritinib 200 mg, twice daily		BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
All Cause Mortality
	Pacritinib, Once Daily		Pacritinib, Twice Daily		Best Available Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/104 (21.2%)		20/107 (18.7%)		20/100 (20%)
Serious Adverse Events
	Pacritinib, Once Daily		Pacritinib, Twice Daily		Best Available Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/104 (46.2%)		50/106 (47.2%)		30/98 (30.6%)
Blood and lymphatic system disorders
Anaemia	5/104 (4.8%)	5	8/106 (7.5%)	8	3/98 (3.1%)	3
Thrombocytopenia	2/104 (1.9%)	2	6/106 (5.7%)	6	2/98 (2%)	2
Febrile neutropenia	1/104 (1%)	1	1/106 (0.9%)	1	2/98 (2%)	2
Neutropenia	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Bone marrow failure	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Haemolysis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Leukocytosis	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Lymphocytic infiltration	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Splenic infarction	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Splenomegaly	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Cardiac disorders
Cardiac failure	1/104 (1%)	1	4/106 (3.8%)	4	2/98 (2%)	2
Atrial fibrillation	3/104 (2.9%)	3	0/106 (0%)	0	3/98 (3.1%)	3
Atrial flutter	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Supraventricular tachycardia	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Cardiac arrest	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Cardiac failure congestive	1/104 (1%)	1	1/106 (0.9%)	1	0/98 (0%)	0
Myocardial infarction	1/104 (1%)	1	0/106 (0%)	0	1/98 (1%)	1
Eye disorders
Conjunctival haemorrhage	0/104 (0%)	0	2/106 (1.9%)	2	0/98 (0%)	0
Gastrointestinal disorders
Oesophageal varices haemorrhage	1/104 (1%)	1	1/106 (0.9%)	1	1/98 (1%)	1
Abdominal pain	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Haemorrholdal haemorrhage	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Melaena	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Abdominal pain upper	1/104 (1%)	1	1/106 (0.9%)	1	0/98 (0%)	0
Diarrhoea	0/104 (0%)	0	2/106 (1.9%)	2	0/98 (0%)	0
Rectal haemorrhage	1/104 (1%)	1	1/106 (0.9%)	1	0/98 (0%)	0
Ascites	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Duodenal ulcer haemorrhage	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Gastric varices haemorrhage	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Gastritis haemorrhagic	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Gastrointestinal haemorrhage	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Gingival bleeding	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Inguinal hernia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Oesophageal haemorrhage	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Pancreatitis acute	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Proctalgia	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Small intestinal haemorrhage	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Tooth socket haemorrhage	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Vomiting	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
General disorders
Disease progression	4/104 (3.8%)	4	3/106 (2.8%)	3	3/98 (3.1%)	3
Pyrexia	2/104 (1.9%)	2	3/106 (2.8%)	3	2/98 (2%)	2
Oedema peripheral	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Fatigue	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
General physical health deterioration	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Mucosal inflammation	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Multi-organ failure	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Sudden death	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Jaundice	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Hepatic cirrhosis	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hepatitis acute	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Immune system disorders
Anaphylactic reaction	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Infections and infestations
Pneumonia	5/104 (4.8%)	5	6/106 (5.7%)	6	4/98 (4.1%)	4
Urinary tract infection	3/104 (2.9%)	3	0/106 (0%)	0	0/98 (0%)	0
Septic shock	2/104 (1.9%)	2	0/106 (0%)	0	1/98 (1%)	1
Sepsis	1/104 (1%)	1	1/106 (0.9%)	1	1/98 (1%)	1
Appendicitis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Cellulitis	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Diverticulitis	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Escherichia bacteraemia	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Infection	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Lower respiratory tract infection	1/104 (1%)	1	0/106 (0%)	0	2/98 (2%)	2
Parainfluenzae virus infection	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Lung infection	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Bronchitis	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Bronchopneumonia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Gastroenteritis	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Pneumonia fungal	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Pyelonephritis acute	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Subcutaneous abscess	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Splenic rupture	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Accidental overdose	1/104 (1%)	1	1/106 (0.9%)	1	0/98 (0%)	0
Post procedural haemorrhage	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Subdural haematoma	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Fall	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hip fracture	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Humerus fracture	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Laceration	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Post procedural haematoma	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/104 (1%)	1	0/106 (0%)	0	1/98 (1%)	1
Failure to thrive	2/104 (1.9%)	2	0/106 (0%)	0	1/98 (1%)	1
Fluid overload	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Dehydration	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Hyperglycaemia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hyperkalaemia	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Hyperuricaemia	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Hypoglycaemia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hyponatraemia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Musculoskeletal and connective tissue disorders
Periarthrtis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Chondrocalcinosis pyrophosphate	0/104 (0%)	0	2/106 (1.9%)	2	0/98 (0%)	0
Back pain	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Groin pain	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Muscle spasms	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Synovitis	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma	0/104 (0%)	0	1/106 (0.9%)	1	2/98 (2%)	2
Squamous cell carcinoma of skin	0/104 (0%)	0	3/106 (2.8%)	3	0/98 (0%)	0
Acute myeloid leukaemia	0/104 (0%)	0	1/106 (0.9%)	1	1/98 (1%)	1
Myelofibrosis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Basal cell carcinoma	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Extranodal marginal zone B-cell lymphoma (MALT type)	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Hodgkin's disease nodular sclerosis stage IV	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Nervous system disorders
Transient ischaemic attack	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Central nervous system lesion	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Cerebral haemorrhage	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Cerebrovascular accident	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Dizziness	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Encephalomalacia	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Haemorrhage intracranial	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Intracranial venous sinus thrombosis	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Lumbar radiculopathy	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Meningorrhagia	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Sciatica	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Neurological decompensation	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Psychiatric disorders
confusional state	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Mental status changes	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Renal and urinary disorders
Renal failure acute	5/104 (4.8%)	5	2/106 (1.9%)	2	2/98 (2%)	2
Bladder perforation	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Proteinuria	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Urinary retention	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Reproductive system and breast disorders
Ovarian rupture	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/104 (1.9%)	2	2/106 (1.9%)	2	1/98 (1%)	1
Respiratory failure	1/104 (1%)	1	1/106 (0.9%)	1	1/98 (1%)	1
Chronic obstructive pulmonary disease	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Dyspnoea	1/104 (1%)	1	0/106 (0%)	0	1/98 (1%)	1
Lung disorder	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Pneumonia aspiration	1/104 (1%)	1	0/106 (0%)	0	1/98 (1%)	1
Pulmonary embolism	1/104 (1%)	1	1/106 (0.9%)	1	0/98 (0%)	0
Pulmonary oedema	2/104 (1.9%)	2	0/106 (0%)	0	0/98 (0%)	0
Acute respiratory failure	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Cough	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Hypoxia	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Organising pneumonia	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Pulmonary arterial hypertension	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Skin and subcutaneous tissue disorders
Petechiae	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Rash	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Dermatitis allergic	0/104 (0%)	0	1/106 (0.9%)	1	0/98 (0%)	0
Vascular disorders
Deep vein Thrombosis	0/104 (0%)	0	0/106 (0%)	0	1/98 (1%)	1
Circulatory collapse	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Haematoma	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Hypotension	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Peripheral vascular disorder	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Shock	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Shock haemorrhagic	1/104 (1%)	1	0/106 (0%)	0	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	Pacritinib, Once Daily		Pacritinib, Twice Daily		Best Available Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/104 (100%)		100/106 (94.3%)		87/98 (88.8%)
Blood and lymphatic system disorders
Thrombocytopenia	34/104 (32.7%)	34	36/106 (34%)	36	23/98 (23.5%)	23
Anaemia	29/104 (27.9%)		25/106 (23.6%)		15/98 (15.3%)	15
Neutropenia	9/104 (8.7%)	9	9/106 (8.5%)	9	6/98 (6.1%)	6
Eye disorders
Conjunctival haemorrhage	3/104 (2.9%)	3	6/106 (5.7%)	6	4/98 (4.1%)	4
Gastrointestinal disorders
Diarrhoea	70/104 (67.3%)	70	51/106 (48.1%)	51	15/98 (15.3%)	15
Nausea	39/104 (37.5%)	39	34/106 (32.1%)	34	11/98 (11.2%)	11
Vomiting	22/104 (21.2%)	22	20/106 (18.9%)	20	5/98 (5.1%)	5
Abdominal pain	20/104 (19.2%)	20	10/106 (9.4%)	10	19/98 (19.4%)	19
Abdmonial distension	3/104 (2.9%)	3	6/106 (5.7%)	6	6/98 (6.1%)	6
Abdominal pain upper	6/104 (5.8%)	6	6/106 (5.7%)	6	6/98 (6.1%)	6
Constipation	15/104 (14.4%)	15	8/106 (7.5%)	8	6/98 (6.1%)	6
Gastrooesophageal reflux disease	6/104 (5.8%)	6	1/106 (0.9%)	1	2/98 (2%)	2
General disorders
Fatigue	18/104 (17.3%)	18	18/106 (17%)	18	16/98 (16.3%)	16
Oedema peripheral	14/104 (13.5%)	14	21/106 (19.8%)	21	15/98 (15.3%)	15
Asthenia	5/104 (4.8%)	5	3/106 (2.8%)	3	6/98 (6.1%)	6
Early satiety	1/104 (1%)	1	3/106 (2.8%)	3	5/98 (5.1%)	5
Pyrexia	11/104 (10.6%)	11	16/106 (15.1%)	16	3/98 (3.1%)	3
Infections and infestations
Upper respiratory tract infection	8/104 (7.7%)	8	11/106 (10.4%)	11	6/98 (6.1%)	6
Pneumonia	8/104 (7.7%)	8	9/106 (8.5%)	9	4/98 (4.1%)	4
Urinary tract infection	8/104 (7.7%)	8	4/106 (3.8%)	4	2/98 (2%)	2
Bronchitis	3/104 (2.9%)	3	6/106 (5.7%)	6	3/98 (3.1%)	3
Injury, poisoning and procedural complications
Contusion	7/104 (6.7%)	7	10/106 (9.4%)	10	8/98 (8.2%)	8
Fall	7/104 (6.7%)	7	5/106 (4.7%)	5	3/98 (3.1%)	3
Investigations
Weight decreased	4/104 (3.8%)	4	7/106 (6.6%)	7	3/98 (3.1%)	3
Electrocardiogram QT prolonged	6/104 (5.8%)	6	2/106 (1.9%)	2	2/98 (2%)	2
Metabolism and nutrition disorders
Decreased appetite	13/104 (12.5%)	13	13/106 (12.3%)	13	11/98 (11.2%)	11
Hyperuricaemia	6/104 (5.8%)	6	3/106 (2.8%)	3	1/98 (1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	8/104 (7.7%)	8	9/106 (8.5%)	9	3/98 (3.1%)	3
Bone pain	5/104 (4.8%)	5	7/106 (6.6%)	7	7/98 (7.1%)	7
Pain in extremity	7/104 (6.7%)	7	10/106 (9.4%)	10	6/98 (6.1%)	6
Back pain	6/104 (5.8%)	6	5/106 (4.7%)	5	3/98 (3.1%)	3
Myalgia	1/104 (1%)	1	7/106 (6.6%)	7	2/98 (2%)	2
Nervous system disorders
Dizziness	15/104 (14.4%)	15	16/106 (15.1%)	16	5/98 (5.1%)	5
Dysgeusia	8/104 (7.7%)	8	8/106 (7.5%)	8	0/98 (0%)	0
Headache	6/104 (5.8%)	6	9/106 (8.5%)	9	5/98 (5.1%)	5
Psychiatric disorders
Insomnia	12/104 (11.5%)	12	10/106 (9.4%)	10	4/98 (4.1%)	4
Renal and urinary disorders
Renal failure acute	6/104 (5.8%)	6	3/106 (2.8%)	3	2/98 (2%)	2
Respiratory, thoracic and mediastinal disorders
Epistaxis	11/104 (10.6%)	11	13/106 (12.3%)	13	13/98 (13.3%)	13
Cough	11/104 (10.6%)	11	9/106 (8.5%)	9	10/98 (10.2%)	10
Dyspnoea	9/104 (8.7%)	9	11/106 (10.4%)	11	9/98 (9.2%)	9
Dyspnoea exertional	2/104 (1.9%)	2	6/106 (5.7%)	6	4/98 (4.1%)	4
Pleural effusion	6/104 (5.8%)	6	1/106 (0.9%)	1	2/98 (2%)	2
Skin and subcutaneous tissue disorders
Pruritus	10/104 (9.6%)	10	11/106 (10.4%)	11	6/98 (6.1%)	6
Rash	6/104 (5.8%)	6	8/106 (7.5%)	8	5/98 (5.1%)	5
Night sweats	8/104 (7.7%)	8	8/106 (7.5%)	8	6/98 (6.1%)	6
Purpura	0/104 (0%)	0	7/106 (6.6%)	7	0/98 (0%)	0
Rash maculo-papular	1/104 (1%)	1	6/106 (5.7%)	6	0/98 (0%)	0
Vascular disorders
Haematoma	3/104 (2.9%)	3	6/106 (5.7%)	6	2/98 (2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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