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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03165734




Registration number
NCT03165734
Ethics application status
Date submitted
17/05/2017
Date registered
24/05/2017
Date last updated
17/05/2024

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
Timepoint [1] 0 0
From baseline at 24 weeks
Primary outcome [2] 0 0
Total Symptom Score (TSS) (excluding tiredness)
Timepoint [2] 0 0
From baseline at Week 24
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
until 2.5 years after the date of randomization
Secondary outcome [2] 0 0
Patient Global Impression of Change (PGIC) assessed at Week 24
Timepoint [2] 0 0
End of Week 12 to 2 years following Week 24 visit
Secondary outcome [3] 0 0
To compare the safety of pacritinib versus P/C therapy
Timepoint [3] 0 0
Randomization through 30 after last treatment

Eligibility
Key inclusion criteria
Diagnosis and Inclusion Criteria

1. Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF (as
defined by Tefferi and Vardiman 2008

2. Platelet count of <50,000/µL at Screening (Day -35 to Day -3)

3. Dynamic International Prognostic Scoring System 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.The TSS criteria need only to be met on a single day.

6. Age =18 years

7. Eastern Cooperative Oncology Group performance status 0 to 2

8. Peripheral blast count of <10% throughout the Screening period prior to randomization

9. Absolute neutrophil count of =500/µL

10. Left ventricular cardiac ejection fraction of =50% by echocardiogram or multigated
acquisition scan

11. 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),
total bilirubin =4 x ULN (in cases where total bilirubin is elevated, direct bilirubin
=4 × ULN, is required) and creatinine =2.5 mg/dL

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

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

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

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

16. Provision of signed informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
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 allogeneic stem cell

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. Prior treatment with more than one JAK2 inhibitor

8. Prior treatment with with ruxolitinib, if BOTH of the following conditions are met:

i. exposure to higher-dose ruxolitinib (>10 mg daily) within 120 days prior to
treatment Day 1 AND ii. total duration of treatment with higher-dose ruxolitinib (>10
mg daily) was >90 days, from first to last exposure (i.e., this 90-day period starts
on the date of first administration of ruxolitinib at a total daily dose of >10 mg and
continues for 90 calendar days, regardless of whether higher-dose ruxolitinib is
administered continuously or intermittently).

9. Prior treatment with any JAK2 inhibitor other than ruxolitinib, irrespective of dose,
with a duration of >90 days. 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.

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

11. Systemic treatment with a strong cytochrome P450 3A4 inhibitor or a strong cytochrome
P450 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

12. 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 (eg, surgery, trauma, or
injury)

13. 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-VEGF) agents, and daily use of
cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs)
within 14 days prior to treatment Day 1

14. 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

15. 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.

16. Any history of CTCAE grade =2 cardiac dysrhythmias within 6 months prior to treatment
Day 1. Patients with non-corrected QT interval 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.

17. QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors
that increase the risk for QT interval prolongation (eg, hypokalemia [defined as serum
potassium <3.0 mEq/L that is persistent and refractory to correction], or history of
long QT interval syndrome).

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

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

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

21. Other malignancy within 3 years prior to treatment Day 1. The following patients may
be eligible despite having had a malignancy within the prior 3 years: patients with
curatively treated squamous or basal cell carcinoma of the skin; patients with
curatively treated non-invasive cancers; patients with 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; and patients with curatively
treated non-metastatic prostate cancer with negative PSA.

22. 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

23. Known seropositivity for human immunodeficiency (HIV) virus. For patients in France,
Czech Republic, and Italy only: testing for HIV is required during Screening.

24. Known active hepatitis A, B, or C virus infection. For patients in France, Czech
Republic and Italy only: testing for hepatitis B and C is required during Screening.

25. Women who are pregnant or lactating

26. Concurrent enrollment in another interventional trial

27. Severe thrombocytopenia due to vitamin B12 deficiency, folate deficiency, or viral
infection in the opinion of the investigator

28. Known hypersensitivity to pacritinib or any of the following inactive ingredients:
microcrystalline cellulose, polyethylene glycol, and magnesium stearate; any
contraindication to the "physician's choice" medicinal product selected by the
investigator to be used as the comparator or to loperamide or equivalent antidiarrheal
medication

29. Persons deprived of their liberty by a judicial or administrative decision

30. Persons subject to legal protection measures or unable to express their consent

31. Temporarily incapacitated persons

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
26/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
399
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
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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Colorado
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Connecticut
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United States of America
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District of Columbia
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United States of America
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Florida
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Illinois
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Kansas
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Missouri
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Nevada
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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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Bosnia and Herzegovina
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Banja Luka
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Bosnia and Herzegovina
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Sarajevo
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Bulgaria
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Pleven
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Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Bulgaria
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Varna
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Alberta
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British Columbia
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Amiens
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Nîmes
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Pessac
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Pierre Benite
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Poitiers
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Tbilisi
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Cologne
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Halle
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Minden
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Munich
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Germany
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Ulm
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Budapest
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Hungary
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Debrecen
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Kaposvár
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Kecskemét
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Hungary
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Nyíregyháza
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Hungary
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Székesfehérvár
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Maharashtra
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Bengaluru
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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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Israel
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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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Brescia
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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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Milan
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Italy
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Monza
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Italy
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Naples
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Italy
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Novara
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Italy
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Palermo
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Italy
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Pavia
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Italy
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Rimini
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Italy
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Rome
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Italy
State/province [86] 0 0
Turin
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Italy
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Udine
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Italy
State/province [88] 0 0
Varese
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Busan
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Korea, Republic of
State/province [90] 0 0
Daegu
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Seoul
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Poland
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Bialystok
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Katowice
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Lublin
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Rzeszów
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Torun
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Warsaw
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Wroclaw
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Lódz
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Romania
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Brasov
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Romania
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Bucharest
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Romania
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Cluj-Napoca
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Russian Federation
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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
State/province [118] 0 0
Pamplona
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Spain
State/province [119] 0 0
Salamanca
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Spain
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Seville
Country [121] 0 0
Spain
State/province [121] 0 0
Valencia
Country [122] 0 0
Ukraine
State/province [122] 0 0
Cherkasy
Country [123] 0 0
Ukraine
State/province [123] 0 0
Dnipro
Country [124] 0 0
Ukraine
State/province [124] 0 0
Ivano-Frankivs'k
Country [125] 0 0
Ukraine
State/province [125] 0 0
Kharkiv
Country [126] 0 0
Ukraine
State/province [126] 0 0
Kyiv
Country [127] 0 0
Ukraine
State/province [127] 0 0
Lviv
Country [128] 0 0
Ukraine
State/province [128] 0 0
Poltava
Country [129] 0 0
United Kingdom
State/province [129] 0 0
South Yorkshire
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Glasgow
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Gloucester
Country [132] 0 0
United Kingdom
State/province [132] 0 0
London
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Manchester
Country [134] 0 0
United Kingdom
State/province [134] 0 0
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 399 patients in total will be
enrolled, randomized 2:1 to either pacritinib (approximately 266 patients) or to P/C therapy
(approximately 133 patients)

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

Intervention/treatment: Drug-Pacritinib
Trial website
https://clinicaltrials.gov/ct2/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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03165734