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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03165734




Registration number
NCT03165734
Ethics application status
Date submitted
17/05/2017
Date registered
24/05/2017
Date last updated
29/04/2021

Titles & IDs
Public title
A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
Scientific title
A Randomized, Controlled Phase 3 Study of Pacritinib Versus Physician's Choice in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Severe Thrombocytopenia (Platelet Count <50,000/µL)(PACIFICA)
Secondary ID [1] 0 0
PAC303
Secondary ID [2] 0 0
PAC203/PAC303
Universal Trial Number (UTN)
Trial acronym
PACIFICA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
Post-polycythemia Vera Myelofibrosis 0 0
Post-essential Thrombocythemia Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pacritinib
Treatment: Drugs - Physician's Choice medications

Experimental: Pacritinib 200 mg BID - To receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food

Active Comparator: Physician's Choice (P/C) therapy - The Physician's Choice (P/C) therapy (limited to single drugs from the following list: corticosteroids, hydroxyurea, danazol, or low-dose ruxolitinib). The proposed P/C regimen for a patient must be selected prior to randomization.


Treatment: Drugs: Pacritinib
Oral administration. Supplied in capsules containing 100 mg (as the free base) in red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000. Each capsule contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base

Treatment: Drugs: Physician's Choice medications
Physician's Choice medications will be selected and administered according to the investigator's judgement. Investigators can select individual P/C agents but cannot combine agents or give them sequentially.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Spleen volume - To compare the efficacy of pacritinib with that of physician's choice (P/C) therapy, as assessed by the proportion of patients achieving a =35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans
Timepoint [1] 0 0
From baseline to 24 weeks
Secondary outcome [1] 0 0
Total Symptom Score (TSS) - To compare the efficacy of pacritinib with P/C therapy, as assessed by the proportion of patients achieving a =50% reduction in Total Symptom Score (TSS)
Timepoint [1] 0 0
Between baseline and Week 24
Secondary outcome [2] 0 0
Overall Survival (OS) - To compare the overall survival (OS) of patients treated with pacritinib versus those treated with P/C
Timepoint [2] 0 0
until 2.5 years after the date of randomization
Secondary outcome [3] 0 0
Patient Global Impression of Change (PGIC) assessed at Week 24 - To compare the percentage of patients who self-assess as "very much improved" or "much improved" as measured by the Patient Global Impression of Change (PGIC) in patients treated with pacritinib versus those treated with P/C
Timepoint [3] 0 0
End of Week 12 to 2 years following Week 24 visit
Secondary outcome [4] 0 0
To compare the safety of pacritinib versus P/C therapy - Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment with pacritinib and/or physician's choice therapy.
Timepoint [4] 0 0
Randomization through 30 after last treatment

Eligibility
Key inclusion criteria
Diagnosis and Inclusion Criteria

1. PMF, PPV-MF, or PET-MF (Tefferi and Vandiman 2008)

2. Average platelet count of <50,000/µL at Screening (Day -35 to Day -3) based on two
measurements taken on different days; both measurements must be <50,000/µL

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

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

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

6. If the patient has received prior JAK2 inhibitor treatment, this treatment must meet
at least one of the following criteria:

1. Prior treatment with any JAK2 inhibitor, irrespective of dose, with a duration of
90 days or less. The 90-day period starts on the date of first administration of
JAK2 inhibitor therapy and continues for 90 calendar days, regardless of whether
therapy is administered continuously or intermittently during that interval.

2. Prior treatment with ruxolitinib, at no more than 10 mg total daily dose on any
day, with a duration of 180 days or less. The 180-day period starts on the date
of first ruxolitinib administration and continues for 180 calendar days,
regardless of whether therapy is administered continuously or intermittently
during that interval.The patient may not have received >10 mg of ruxolitinib on
any day during that interval

7. Age =18 years

8. Eastern Cooperative Oncology Group performance status 0 to 2

9. Peripheral blast count of <10% throughout the Screening period and at baseline

10. Absolute neutrophil count of =500/µL

11. Left ventricular cardiac ejection fraction of =50% by echocardiogram or multigated
acquisition (MUGA) scan

12. 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

13. Adequate coagulation defined by prothrombin time/international normalized ratio and
partial thromboplastin time =1.5 × ULN

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

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

16. Able to understand and willing to complete symptom assessments using a
patient-reported outcome instrument

17. Provision of signed informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Life expectancy <6 months

2. Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing
to complete other approved available therapy including 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. Treatment with any MF-directed therapy within 14 days prior to treatment Day 1

7. Any prior treatment with more than one JAK2 inhibitor

8. Treatment with an experimental therapy within 28 days prior to treatment Day 1

9. Systemic treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450)
inducer within 14 days prior to treatment Day 1. Shorter washout periods may be
permitted with approval of the Medical Monitor, provided that the washout period is at
least five half-lives of the drug prior to treatment Day 1

10. Significant recent bleeding history defined as National Cancer Institute Common
Terminology Criteria for Adverse Events (CTCAE) grade =2 within 3 months prior to
treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or
injury)

11. Systemic treatment with medications that increase the risk of bleeding, including
anticoagulants, antiplatelet agents (except for aspirin dosages of =100 mg per day),
anti-vascular endothelial growth factor (anti-vascular endothelial growth factor
[anti-VEGF]) agents, and daily use of cyclooxygenase-1 (COX-1) inhibiting nonsteroidal
anti- inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1

12. Systemic treatment with medications that can prolong the QT interval within 14 days
prior to treatment Day 1. Shorter washout periods may be permitted with approval of
the Medical Monitor, provided that the washout period is at least five half-lives of
the drug prior to treatment Day 1

13. Any history of CTCAE grade =2 non-dysrhythmia cardiac conditions within 6 months prior
to treatment Day 1. Patients with asymptomatic grade 2 non- dysrhythmia cardiovascular
conditions may be considered for inclusion, with the approval of the Medical Monitor,
if stable and unlikely to affect patient safety.

14. Any history of CTCAE grade =2 cardiac dysrhythmias within 6 months prior to treatment
Day 1. 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. QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors
that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia
[defined as serum potassium <3.0 mEq/L that is persistent and refractory to
correction], or history of long QT interval syndrome

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

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

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

19. Other malignancy within 3 years prior to treatment Day 1, other than curatively
treated basal cell or squamous cell skin or corneal cancer; curatively treated
carcinoma in situ of the cervix; organ-confined prostate cancer with prostate-specific
antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low,
Low, or Favorable Intermediate; curatively treated non-metastatic prostate cancer with
negative PSA; or in situ breast carcinoma after complete surgical resection

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

21. Known seropositivity for human immunodeficiency virus

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

23. Women who are pregnant or lactating

24. Concurrent enrollment in another interventional trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Alfred Hospital, Malignant Hematology and Stem Cell Transplantation Service - Melbourne
Recruitment hospital [3] 0 0
The Perth Blood Institute - Perth
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
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United States of America
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District of Columbia
Country [7] 0 0
United States of America
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Florida
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United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
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United States of America
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Massachusetts
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Michigan
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Utah
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Washington
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Belarus
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Gomel
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Belarus
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Grodno
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Belarus
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Minsk
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Bulgaria
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Pleven
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Plovdiv
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Bulgaria
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Sofia
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Varna
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Canada
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Alberta
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Canada
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British Columbia
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Brno
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Olomouc
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Pilsen
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Prague
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Poitiers
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Germany
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Cologne
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Halle
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Germany
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Ulm
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Budapest
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Debrecen
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Haifa
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Jerusalem
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Israel
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Kfar Saba
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Petah-Tikva
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Israel
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Tel Aviv
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Italy
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Bari
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Italy
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Bologna
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Italy
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Florence
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Italy
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Forlì
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Italy
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Monza
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Italy
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Palermo
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Italy
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Pavia
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Rimini
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Italy
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Rome
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Varese
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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Seoul
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Kraków
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Rzeszów
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Torun
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Moscow
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Russian Federation
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Pyatigorsk
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Russian Federation
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Saint Petersburg
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Russian Federation
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Samara
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Russian Federation
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Ufa
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Russian Federation
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Volgograd
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Serbia
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Belgrade
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Serbia
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Novi Sad
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Spain
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Barcelona,
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Murcia
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Valencia
Country [101] 0 0
Ukraine
State/province [101] 0 0
Cherkasy
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Ukraine
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Dnipro
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Ukraine
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Ivano-Frankivs'k
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Poltava
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United Kingdom
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South Yorkshire
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United Kingdom
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Glasgow
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London
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United Kingdom
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Manchester
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United Kingdom
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CTI BioPharma
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PSI CRO
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID
of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe
thrombocytopenia (platelet count <50,000/µL). Approximately 348 patients in total will be
enrolled, randomized 2:1 to either pacritinib (approximately 232 patients) or to P/C therapy
(approximately 116 patients)

Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/
Post-essential Thrombocythemia Myelofibrosis

Intervention/treatment: Drug-Pacritinib
Trial website
https://clinicaltrials.gov/show/NCT03165734
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Simran Bedi Singh
Address 0 0
CTI BioPharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Simran Bedi Singh
Address 0 0
Country 0 0
Phone 0 0
206-272-4454
Fax 0 0
Email 0 0
ssingh@ctibiopharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03165734