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Trial details imported from ClinicalTrials.gov

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




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

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
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
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oregon
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Utah
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Belarus
State/province [26] 0 0
Gomel
Country [27] 0 0
Belarus
State/province [27] 0 0
Grodno
Country [28] 0 0
Belarus
State/province [28] 0 0
Minsk
Country [29] 0 0
Bosnia and Herzegovina
State/province [29] 0 0
Banja Luka
Country [30] 0 0
Bosnia and Herzegovina
State/province [30] 0 0
Sarajevo
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Pleven
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Plovdiv
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Sofia
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Varna
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Newfoundland and Labrador
Country [38] 0 0
Canada
State/province [38] 0 0
Nova Scotia
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Czechia
State/province [41] 0 0
Brno
Country [42] 0 0
Czechia
State/province [42] 0 0
Olomouc
Country [43] 0 0
Czechia
State/province [43] 0 0
Pilsen
Country [44] 0 0
Czechia
State/province [44] 0 0
Prague
Country [45] 0 0
France
State/province [45] 0 0
Amiens
Country [46] 0 0
France
State/province [46] 0 0
Marseille
Country [47] 0 0
France
State/province [47] 0 0
Nîmes
Country [48] 0 0
France
State/province [48] 0 0
Paris
Country [49] 0 0
France
State/province [49] 0 0
Pessac
Country [50] 0 0
France
State/province [50] 0 0
Pierre Benite
Country [51] 0 0
France
State/province [51] 0 0
Poitiers
Country [52] 0 0
France
State/province [52] 0 0
Strasbourg
Country [53] 0 0
France
State/province [53] 0 0
Toulouse
Country [54] 0 0
Georgia
State/province [54] 0 0
Tbilisi
Country [55] 0 0
Germany
State/province [55] 0 0
Cologne
Country [56] 0 0
Germany
State/province [56] 0 0
Halle
Country [57] 0 0
Germany
State/province [57] 0 0
Minden
Country [58] 0 0
Germany
State/province [58] 0 0
Munich
Country [59] 0 0
Germany
State/province [59] 0 0
Ulm
Country [60] 0 0
Hungary
State/province [60] 0 0
Budapest
Country [61] 0 0
Hungary
State/province [61] 0 0
Debrecen
Country [62] 0 0
Hungary
State/province [62] 0 0
Kaposvár
Country [63] 0 0
Hungary
State/province [63] 0 0
Kecskemét
Country [64] 0 0
Hungary
State/province [64] 0 0
Nyíregyháza
Country [65] 0 0
Hungary
State/province [65] 0 0
Székesfehérvár
Country [66] 0 0
India
State/province [66] 0 0
Maharashtra
Country [67] 0 0
India
State/province [67] 0 0
Bengaluru
Country [68] 0 0
Israel
State/province [68] 0 0
Haifa
Country [69] 0 0
Israel
State/province [69] 0 0
Jerusalem
Country [70] 0 0
Israel
State/province [70] 0 0
Kfar Saba
Country [71] 0 0
Israel
State/province [71] 0 0
Petah-Tikva
Country [72] 0 0
Israel
State/province [72] 0 0
Tel Aviv
Country [73] 0 0
Italy
State/province [73] 0 0
Bari
Country [74] 0 0
Italy
State/province [74] 0 0
Bologna
Country [75] 0 0
Italy
State/province [75] 0 0
Brescia
Country [76] 0 0
Italy
State/province [76] 0 0
Florence
Country [77] 0 0
Italy
State/province [77] 0 0
Forlì
Country [78] 0 0
Italy
State/province [78] 0 0
Milan
Country [79] 0 0
Italy
State/province [79] 0 0
Monza
Country [80] 0 0
Italy
State/province [80] 0 0
Naples
Country [81] 0 0
Italy
State/province [81] 0 0
Novara
Country [82] 0 0
Italy
State/province [82] 0 0
Palermo
Country [83] 0 0
Italy
State/province [83] 0 0
Pavia
Country [84] 0 0
Italy
State/province [84] 0 0
Rimini
Country [85] 0 0
Italy
State/province [85] 0 0
Rome
Country [86] 0 0
Italy
State/province [86] 0 0
Turin
Country [87] 0 0
Italy
State/province [87] 0 0
Udine
Country [88] 0 0
Italy
State/province [88] 0 0
Varese
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Busan
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Daegu
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Seoul
Country [92] 0 0
Poland
State/province [92] 0 0
Bialystok
Country [93] 0 0
Poland
State/province [93] 0 0
Gdansk
Country [94] 0 0
Poland
State/province [94] 0 0
Katowice
Country [95] 0 0
Poland
State/province [95] 0 0
Kraków
Country [96] 0 0
Poland
State/province [96] 0 0
Lublin
Country [97] 0 0
Poland
State/province [97] 0 0
Nowy Sacz
Country [98] 0 0
Poland
State/province [98] 0 0
Rzeszów
Country [99] 0 0
Poland
State/province [99] 0 0
Torun
Country [100] 0 0
Poland
State/province [100] 0 0
Warsaw
Country [101] 0 0
Poland
State/province [101] 0 0
Wroclaw
Country [102] 0 0
Poland
State/province [102] 0 0
Lódz
Country [103] 0 0
Romania
State/province [103] 0 0
Brasov
Country [104] 0 0
Romania
State/province [104] 0 0
Bucharest
Country [105] 0 0
Romania
State/province [105] 0 0
Cluj-Napoca
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Moscow
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Pyatigorsk
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Saint Petersburg
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Samara
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Ufa
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Volgograd
Country [112] 0 0
Serbia
State/province [112] 0 0
Belgrade
Country [113] 0 0
Serbia
State/province [113] 0 0
Novi Sad
Country [114] 0 0
Spain
State/province [114] 0 0
Barcelona,
Country [115] 0 0
Spain
State/province [115] 0 0
Barcelona
Country [116] 0 0
Spain
State/province [116] 0 0
Madrid
Country [117] 0 0
Spain
State/province [117] 0 0
Murcia
Country [118] 0 0
Spain
State/province [118] 0 0
Pamplona
Country [119] 0 0
Spain
State/province [119] 0 0
Salamanca
Country [120] 0 0
Spain
State/province [120] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03165734