A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Primary Myelofibrosis Clinical Trial

— PACIFICA  

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03165734
• Other study ID #: PAC203/PAC303
• Secondary ID: PAC303
• Status: Recruiting
• Phase: Phase 3
• Start date: June 26, 2017
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: CTI BioPharma
• Contact: Simran Bedi Singh
• Phone: 206-272-4454
• Email: simran.singh[@]sobi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

The study is a randomized, controlled phase 3 study comparing the efficacy of pacritinib with P/C therapy in patients with PMF, PPV-MF, or PET-MF (Dynamic International Prognostic Scoring System [DIPSS] risk score of Intermediate-1 to High-Risk), who have had had no or limited exposure to any JAK2 inhibitor or are JAK2 inhibitor-naive, and who have severe thrombocytopenia (platelet count <50,000/µL). This study was designed to use the pacritinib 200 mg BID dose, which was determined to be the optimal dose based on dose- and exposure-response analyses conducted using all available data, including the dosing data from the previous portion of this study. Patients will be randomized 2:1 to receive pacritinib 200 mg BID or the 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. Randomization will be stratified by prior JAK2 inhibitor therapy (yes/no) and P/C therapy selected prior to randomization. Prior JAK2 inhibitor therapy will be defined as any duration of treatment with a JAK2 inhibitor, such as ruxolitinib, fedratinib, or momelotinib. To be eligible, patients are not allowed to have been treated with more than one JAK2 inhibitor. Assigned treatment will continue until the patient experiences progressive disease or intolerable AEs, withdraws consent, or initiates new MF-directed therapy. No study treatment crossover will be allowed at any time. All patients should complete all visit procedures through Week 24, including patients who stop treatment or have protocol-defined progressive disease prior to Week 24, unless the patient withdraws consent for study procedures, dies, undergoes splenic irradiation or splenectomy, initiates any non-protocol-directed anti-MF treatment, or the study is terminated. In addition to the above, patients will be considered to have discontinued treatment if pacritinib or P/C therapy is held for >28 consecutive days due to treatment toxicity, or if treatment is discontinued for lack of efficacy, or at the request of the principal investigator or the patient. Following the Week 24 assessment, patients who are benefiting from therapy will be allowed to continue receiving the assigned treatment (pacritinib or P/C) until the patient experiences progressive disease, intolerable AEs, withdraws consent, or initiates new MF-directed therapy. All randomized patients will be followed for survival for 2.5 years from the date of randomization unless consent for follow-up is withdrawn.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 399
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• 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
• 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.

Locations

Country	Name	City	State
Australia	Alfred Hospital, Malignant Hematology and Stem Cell Transplantation Service	Melbourne	Victoria
Australia	The Perth Blood Institute	Perth	Western Australia
Australia	Westmead Hospital	Sydney	New South Wales
Belarus	Republican Research Center for Radiation Medicine and Human Ecology	Gomel
Belarus	Grodno University Hospital	Grodno
Belarus	Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology	Minsk
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	University Clinical Center of Sarajevo	Sarajevo
Bulgaria	University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"	Pleven
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment - Sofia, part of Military Medical Academy	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Sveta Marina"	Varna
Canada	Tom Baker Cancer Center, Internal Medicine/Hematology	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Nova Scotia Health Authority, Centre for Clinical Research	Halifax	Nova Scotia
Canada	Jewish General Hospital; Clinical Research Unit	Montreal	Quebec
Canada	Eastern Regional Health Authority	Saint John's	Newfoundland and Labrador
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Providence Hematology - Vancouver	Vancouver	British Columbia
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Plzen	Pilsen
Czechia	University Hospital Kralovske Vinohrady, Clinic of Internal Hematology	Prague
France	CHU Hôpital Amiens Sud	Amiens
France	La Conception Hospital	Marseille
France	CHU de Nimes - Hopital Universitaire Caremeau	Nîmes
France	Hôpital Saint-Louis	Paris
France	CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque	Pessac
France	Centre Hospitalier Lyon-Sud	Pierre Benite
France	University Hospital Center of Poitiers	Poitiers
France	Hautepierre Hospital	Strasbourg
France	Centre Hospitalier de Toulouse- Hôpital Purpan	Toulouse
Georgia	JSC K. Eristavi National Center For Experimental and Clinical Surgery	Tbilisi
Georgia	LTD M.Zodelava's Hematology Center, Department of Hematology	Tbilisi
Georgia	LTD National Institute of Endocrinology	Tbilisi
Georgia	LTD S.Khechinashvili University Hospital	Tbilisi
Georgia	Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTD	Tbilisi
Georgia	Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC	Tbilisi
Germany	University Hospital Cologne, Department of Internal Medicine I,	Cologne
Germany	University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology	Halle
Germany	Johannes Wesling Hospital Minden, Department of Oncology and Hematology	Minden
Germany	Hospital rechts der Isar, Department of Internal Medicine III, Hematology and Oncology	Munich
Germany	University Hospital Ulm, Center for Internal Medicine,	Ulm
Hungary	Semmelweis University SE ÁOK I. sz. Belgyógyászati Klinika	Budapest
Hungary	University of Debrecen Clinical Center (Debreceni Egyetem Klinikai Központ)	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Hungary	Bacs-Kiskun County Hospital, 2nd Department of Internal Medicine	Kecskemét
Hungary	Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology	Nyíregyháza
Hungary	Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine I	Székesfehérvár
India	St. John's Medical College Hospital	Bengaluru
Israel	Lady Davis Carmel Medical Center, Department of Hematology,	Haifa
Israel	Hadassah Medical Center, Department of Hematology,	Jerusalem
Israel	Meir Medical Center, Hematology Institute and Blood Bank	Kfar Saba
Israel	Rabin Medical Center, Clinic for Myeloproliferative Disorders	Petah-Tikva
Israel	The Tel Aviv Sourasky Medical Center, Department of Internal Medicine	Tel Aviv
Italy	Cancer Institute "Giovanni Paolo II", IRCCS	Bari
Italy	Polyclinic S. Orsola-Malpighi	Bologna
Italy	ASST Spedali Civili Brescia, Hematology Unit	Brescia
Italy	Azienda Ospedaliero-Universitaria Careggi	Florence
Italy	Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS	Forlì
Italy	Maggiore Polyclinic Hospital, Fondazione IRCCS Ca' Granda	Milan
Italy	ASST Monza - Ospedale San Gerardo	Monza
Italy	University Hospital "Federico II"	Naples
Italy	University Hospital "Maggiore della Carita" of Novara	Novara
Italy	United Hospitals Villa Sofia Cervello	Palermo
Italy	Polyclinic San Matteo, IRCCS	Pavia
Italy	Hospital "Infermi" of Rimini	Rimini
Italy	Umberto I Polyclinic of Rome	Rome
Italy	University Polyclinic Foundation "Agostino Gemelli"	Rome
Italy	ASST Sette Laghi Hospital	Varese
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Mary's Hospital	Seoul
Poland	University Teaching Hospital in Bialystok	Bialystok
Poland	University Clinical Center in Gdansk	Gdansk
Poland	Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice, Department of Hematology and Bone Marrow Transplantation	Katowice
Poland	Pratia Oncology Katowice	Katowice
Poland	University Hospital in Krakow	Kraków
Poland	Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz	Lódz
Poland	Independent Public Teaching Hospital No.1 in Lublin, Department of Hematooncology, Bone Marrow Transplantation and Chemotherapy	Lublin
Poland	Jedrzej Sniadecki Specialist Hospital in Nowy Sacz, Department of Hematology	Nowy Sacz
Poland	Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology,	Rzeszów
Poland	Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka	Torun
Poland	Institute of Hematology and Transfusion Medicine, Teaching Department of Hematology	Warsaw
Poland	Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation	Wroclaw
Romania	Onco Card Srl	Brasov
Romania	Coltea Clinical Hospital	Bucharest
Romania	Fundeni Clinical Institute	Bucharest
Romania	Prof. Dr. Ion Chiricuta" Institute of Oncology	Cluj-Napoca
Russian Federation	City Clinical Hospital #40	Moscow
Russian Federation	City Clinical Hospital n.a. V.V. Veresaev of the Moscow City Health	Moscow
Russian Federation	S.P. Botkin City Clinical Hospital	Moscow
Russian Federation	Clinic UZI 4D, LLC	Pyatigorsk
Russian Federation	Research Institute of Hematology and Transfusiology	Saint Petersburg
Russian Federation	S.M. Kirov Military Medical Academy, Department and Clinic for Intermediate-Level Training in Internal Medicine, Hematology Division	Saint Petersburg
Russian Federation	V.A. Almazov North-West Federal Medical Research Center, Institute of Oncology and Hematology, Scientific Department of Clinical Oncology	Saint Petersburg
Russian Federation	V.D. Seredavin Samara Regional Clinical Hospital, Department of Hematology	Samara
Russian Federation	Bashkiria State Medical University, Department of Internal Medicine	Ufa
Russian Federation	Volgograd Regional Clinical Oncology Center	Volgograd
Serbia	Clinical Center of Serbia, Clinic of Hematology	Belgrade
Serbia	Clinical Center of Vojvodina, Clinic of Hematology	Novi Sad
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Hospital del Mar	Barcelona,
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	University Hospital 12 de Octubre, Department of Hematology	Madrid
Spain	Morales Meseguer University General Hospital, Department of Hematology and Hemotherapy	Murcia
Spain	Clínica Universidad de Navarra	Pamplona
Spain	University Clinical Hospital of Salamanca, Department of Hematology	Salamanca
Spain	University Hospital Virgen del Rocio (HUVR)	Seville
Spain	University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology	Valencia
Ukraine	Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council, Regional Treatment and Diagnostic Hematology Center, Department of Hematology	Cherkasy
Ukraine	City Clinical Hospital #4" under Dnipro City Council	Dnipro
Ukraine	Regional Clinical Hospital, Department of Hematology,	Ivano-Frankivs'k
Ukraine	Communal Non-profit enterprise "Regional Center of Oncology", Department of Hematology	Kharkiv
Ukraine	Kyiv City Clinical Hospital #9, Hematology Department #1	Kyiv
Ukraine	Kyiv Regional Oncology Center, Department of Hematology,	Kyiv
Ukraine	Limited Liability Company "City Doctor"	Kyiv
Ukraine	Institute of Blood Pathology and Transfusion Medicine, Department of Hematology	Lviv
Ukraine	Poltava M.V. Sklifosovskyi Regional Clinical Hospital under Poltava Regional Council, Department of Hematology	Poltava
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Gloucestershire Royal Hospital	Gloucester
United Kingdom	Barts Health NHS Trust - The Royal London Hospital	London
United Kingdom	Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust - Hammersmith Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford
United Kingdom	Royal Hallamshire Hospital, Department of Hematology	Sheffield	South Yorkshire
United States	Michigan Medicine Hematology Clinic-Rogel Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	Regional Cancer Care Associates LLC - CCBD Division	Bethesda	Maryland
United States	University of Alabama at Birmingham, (UAB) Hospital, Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana Farber Cancer Institute, Massachusetts General Hospital	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers (US Oncology/McKesson)	Boulder	Colorado
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Maryland Oncology Hematology, PA- Columbia	Columbia	Maryland
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan-Kettering Cancer Center- Commack	Commack	New York
United States	City of Hope	Duarte	California
United States	Duke University Hospital	Durham	North Carolina
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada- Twain Office	Las Vegas	Nevada
United States	UCLA David Geffen School of Medicine	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	The Sarah Cannon Research Institute-Tennessee Oncology	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan -Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine-Siteman Cancer Center	Saint Louis	Missouri
United States	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah
United States	Mays Cancer Center	San Antonio	Texas
United States	Texas Oncology- San Antonio	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	George Washington University-Medical Faculty Associates	Washington	District of Columbia
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida
United States	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
CTI BioPharma	PSI CRO

Countries where clinical trial is conducted

United States,  Australia,  Belarus,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Czechia,  France,  Georgia,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SVR of =35%	Time to achievement of SVR of =35%	Up to 24 Weeks
Other	Best response in SVR	Best response in SVR by MRI or CT scan	At 24 Weeks
Other	>25% SVR	Proportion of patients achieving >25% SVR	From baseline and at Week 24
Other	Red blood cell (RBC)	Achievement of red blood cell (RBC) transfusion independence at Weeks 12 and 24	Baseline to End of Treatment
Other	hemoglobin level	Improvement in hemoglobin level without transfusion at Weeks 12 and 24	Weeks 12 and 24
Other	platelet count	Improvement in platelet count at Weeks 12 and 24	Weeks 12 and 24
Other	platelet transfusions	Frequency of platelet transfusions at Weeks 12 and 24	Weeks 12 and 24
Other	PROMIS	Improvement in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) v.1.0 - Fatigue from Baseline through Week 24	Baseline to Week 24
Other	Leukemia-free survival (LFS)	Leukemia-free survival (LFS) of patients treated with pacritinib versus P/C therapy	Baseline to Week 24
Other	The percentage of red blood cell transfusion-independent patients achieving a 1 g/dL and a 2 g/dL increase in hemoglobin	The percentage of red blood cell transfusion-independent patients at baseline achieving a 1 g/dL and a 2 g/dL increase in hemoglobin at week 24	Baseline to 24 weeks
Other	The percentage of platelet transfusion-independent patients with improvement in grade of thrombocytopenia	The percentage of platelet transfusion-independent patients at baseline with improvement in grade of thrombocytopenia at week 24	Baseline to 24 weeks
Other	The percentage of transfusion-dependent patients achieving transfusion independence and achieving 50% reduction in transfusion rate	The percentage of transfusion-dependent patients at baseline achieving transfusion independence and achieving 50% reduction in transfusion rate at week 24	Baseline to 24 weeks
Other	Hemaglobin A1c	Changes in hemoglobin A1c	Baseline to Week 24
Other	mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers	Changes in mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers	Baseline to up to 24 Weeks
Other	The proportion of patients who experience a major adverse cardiac event (MACE)	MACE is a composite endpoint that is considered to occur if any of the following TEAEs occur: cardiovascular death, defined as death due to acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular procedures, death due to cardiovascular hemorrhage, or death due to peripheral artery disease; non-fatal myocardial infarction; non-fatal stroke of any classification, including reversible focal neurological defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage	Baseline to up to 24 Weeks
Primary	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	From baseline at 24 weeks
Primary	Total Symptom Score (TSS) (excluding tiredness)	To compare the efficacy of pacritinib compared to P/C therapy, as assessed by the proportion of patients achieving a =50% reduction in Total Symptom Score (TSS). The TSS is the sum of the individual symptom scores for tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under ribs on the left side. Symptoms are ranked 0 (absent) to 10 (worst imaginable)	From baseline at Week 24
Secondary	Overall Survival (OS)	To compare the overall survival (OS) of patients treated with pacritinib versus those treated with P/C	until 2.5 years after the date of randomization
Secondary	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	End of Week 12 to 2 years following Week 24 visit
Secondary	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.	Randomization through 30 after last treatment