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

Primary Myelofibrosis Clinical Trial

— PAC326  

Official title:

A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02055781
• Other study ID #: PERSIST-2 (PAC326)
• Status: Terminated
• Phase: Phase 3
• Start date: February 2014
• Est. completion date: April 2016

Study information

• Verified date: October 2021
• Source: CTI BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 311
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

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

• Palpable splenomegaly = 5 cm on physical examination

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

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

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

• At least 6 months from prior splenic irradiation

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

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

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

Exclusion Criteria:

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

• There is no maximum cumulative prior JAK2 inhibitor treatment

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

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

• Active bleeding that requires hospitalization during the screening period

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

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

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

• Life expectancy < 6 months

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pacritinib

• Best Available Therapy

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Haematology and Oncology Clinics of Australia	Chermside
Australia	Monash Health - Monash Medical Centre	Clayton	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	Perth Blood Institute	Nedlands	Western Australia
Australia	Prince of Wales Hospital	Randwick
Belgium	ZNA - Stuivenberg	Antwerpen
Belgium	AZ Sint Jan Brugge-Oostende AV	Brugge
Belgium	Hopital Brugmann	Brussels
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Centre Hospitalier de Jolimont-Lobbes	Haine-Saint-Paul	Hainaut
Belgium	St Augustinus	Wilrijk
Belgium	UC Louvain	Yvoir
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Czechia	Fakultní nemocnice Brno	Brno	NAP
Czechia	University Hospital Hradec Kralove	Králová
Czechia	Faculty Hospital Olomouc	Olomouc	NAP
Czechia	Fakultní nemocnice Plzen	Plzen	NAP
France	Chu d'Amiens Hopital Sud	Amiens	Cedex 1
France	CHU de CAEN	Caen
France	Centre Hospitalier de Lens	Lens
France	CH de Mulhouse	Mulhouse	Cedex
France	Hopital l'Archet, CHU de Nice	Nice
France	Hôpital Caremeau	Nimes	Cedex 9
France	Saint Antoine Hospital	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU Rennes	Rennes	Cedex 9
France	CHU de Strasbourg	Strasbourg
France	CHU Purpan	Toulouse	Cedex 9
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Charite-Medical University	Berlin
Germany	Gemeinschaftspraxis Hämatologie/Onkologie	Dresden
Germany	University Hospital Essen	Essen
Germany	Uniklinik Freiburg	Freiburg
Germany	Universitatsklinikum Halle (Saale)	Halle (Saale)
Germany	Klinik I fur Innere Medizin, Universitat Koln	Koln
Germany	University Hospital Leipzig	Leipzig
Germany	Städtisches Klinikum München GmbH	Munchen
Germany	University of Munster	Munster
Germany	University Hospital Ulm	Ulm
Hungary	Semmelweis Egyetem AOK	Budapest
Hungary	University of Debrecen, Belgyogyaszati Intezet	Debrecen
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Hungary	Kaposi Mór Oktató Kórház	Kaposvár
Hungary	SZTE II. sz Belgyogyoszati Klinika es Kardiologiai Kozpont	Szeged
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendeloint	Szolnok
Netherlands	University Hospital Maastricht	Maastricht
Netherlands	Erasmus MC	Rotterdam
New Zealand	Auckland District Health Board, Auckland City Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	Canterbury District Health Board	Christchurch
New Zealand	North Shore Hospital	Takapuna
New Zealand	CCDHB - Wellington Hospital	Wellington
Russian Federation	National Haematology Research Center	Moscow
Russian Federation	Republican Hopsital n.a. V.A. Baranov	Petrozavodsk
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	Saratov State Medical University	Saratov	Saratov Region
Russian Federation	Military Medical Academy n.a. S.M. Kirov	St. Petersburg
Russian Federation	Russian Research Institute of Hematology and Transfusiology	St. Petersburg
Russian Federation	Bashkir State Medical University	Ufa	Republic Of Bashkortostan
United Kingdom	Belfast Health and Social Care Trust	Belfast	N. Ireland
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Royal Liverpool University Hospital	Liverpool	Merseyside
United Kingdom	Guy's Hospital	London
United Kingdom	Hammersmith Hosp - ICH NHS Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Oxford University Hospitals NHS Trust	Oxford
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	St Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Center	Boulder	Colorado
United States	Northwestern University	Chicago	Illinois
United States	SCRI-Oncology Hematology Care	Cincinnati	Ohio
United States	Cleveland Clinic-Taussig Cancer Center	Cleveland	Ohio
United States	Texas Onocolgy-Baylor Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	SCRI- Florida Cancer Specialists South Region	Fort Myers	Florida
United States	UTMB Galveston	Galveston	Texas
United States	Indiana University Goshen Cancer Centre	Goshen	Indiana
United States	Green Bay Oncology	Green Bay	Wisconsin
United States	Upstate Oncology Associates	Greenville	South Carolina
United States	Hackensack University	Hackensack	New Jersey
United States	Houston Methodist	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Investigative Clinical Research of Indiana	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Moores Cancer Centre	La Jolla	California
United States	Virginia Cancer Specialists	Leesburg	Virginia
United States	Nebraska Hematology-Oncology, P.C.	Lincoln	Nebraska
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute, Suburban	Louisville	Kentucky
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hematology-Oncology Associates of Northern Jersey	Morristown	New Jersey
United States	Sarah Cannon Research Institute (SCRI)	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine Division of Oncology	Saint Louis	Missouri
United States	SCRI - Florida Cancer Specialists North Region	Saint Petersburg	Florida
United States	Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Siouxland Hematology-Oncology Associates, L.L.P (SHOA)	Sioux City	Iowa
United States	Providence Cancer Institute	Southfield	Michigan
United States	Stanford Cancer Center	Stanford	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	George Washington University- Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Netherlands,  New Zealand,  Russian Federation,  United Kingdom, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spleen Volume Reduction	Proportion of patients achieving a = 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).	Baseline to Week 24
Primary	Total Symptom Score (TSS) Reduction	Proportion of patients achieving a = 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 [absent] to 10 [worst imaginable]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.	Baseline to Week 24