Clinical trial NCT02055781: Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Keywords: Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Primary Myelofibrosis
Polycythemia Vera
Essential Thrombocythemia
Bone Marrow Disease
Hematologic Diseases
Hemorrhagic Disorders
Splenomegaly
Pacritinib
MPN-SAF
MPN-SAF TSS
Anemia
Myeloproliferative Neoplasm
Spleen volume
Thrombocytopenia
SB1518
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2014-02-05
Enrollment: 311
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Spleen Volume Reduction
timeFrame: Baseline to Week 24
measure: Total Symptom Score (TSS) Reduction
timeFrame: Baseline to Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: Moores Cancer Centre
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Washington
country: United States
facility: George Washington University- Medical Faculty Associates
state: District of Columbia
city: Fort Myers
country: United States
facility: SCRI- Florida Cancer Specialists South Region
state: Florida
city: Saint Petersburg
country: United States
facility: SCRI - Florida Cancer Specialists North Region
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Goshen
country: United States
facility: Indiana University Goshen Cancer Centre
state: Indiana
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, L.L.P (SHOA)
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, Suburban
state: Kentucky
city: Ann Arbor
country: United States
facility: St Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Division of Oncology
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Hematology-Oncology, P.C.
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University
state: New Jersey
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Cincinnati
country: United States
facility: SCRI-Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic-Taussig Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Upstate Oncology Associates
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI)
state: Tennessee
city: Dallas
country: United States
facility: Texas Onocolgy-Baylor Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Galveston
country: United States
facility: UTMB Galveston
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital
state: Utah
city: Leesburg
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre
state: Victoria
city: Nedlands
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Chermside
country: Australia
facility: Haematology and Oncology Clinics of Australia
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: Haine-Saint-Paul
country: Belgium
facility: Centre Hospitalier de Jolimont-Lobbes
state: Hainaut
city: Antwerpen
country: Belgium
facility: ZNA - Stuivenberg
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge-Oostende AV
city: Brussels
country: Belgium
facility: Hopital Brugmann
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Wilrijk
country: Belgium
facility: St Augustinus
city: Yvoir
country: Belgium
facility: UC Louvain
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
state: NAP
city: Olomouc
country: Czechia
facility: Faculty Hospital Olomouc
state: NAP
city: Plzeň
country: Czechia
facility: Fakultní nemocnice Plzeň
state: NAP
city: Králová
country: Czechia
facility: University Hospital Hradec Kralove
city: Amiens
country: France
facility: Chu d'Amiens Hopital Sud
state: Cedex 1
city: Nimes
country: France
facility: Hôpital Caremeau
state: Cedex 9
city: Rennes
country: France
facility: CHU Rennes
state: Cedex 9
city: Toulouse
country: France
facility: CHU Purpan
state: Cedex 9
city: Mulhouse
country: France
facility: CH de Mulhouse
state: Cedex
city: Caen
country: France
facility: CHU de CAEN
city: Lens
country: France
facility: Centre Hospitalier de Lens
city: Nice
country: France
facility: Hopital l'Archet, CHU de Nice
city: Paris
country: France
facility: Saint Antoine Hospital
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite-Medical University
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Hämatologie/Onkologie
city: Essen
country: Germany
facility: University Hospital Essen
city: Freiburg
country: Germany
facility: Uniklinik Freiburg
city: Halle (Saale)
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Koln
country: Germany
facility: Klinik I fur Innere Medizin, Universitat Koln
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Munchen
country: Germany
facility: Städtisches Klinikum München GmbH
city: Munster
country: Germany
facility: University of Munster
city: Ulm
country: Germany
facility: University Hospital Ulm
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK
city: Debrecen
country: Hungary
facility: University of Debrecen, Belgyogyaszati Intezet
city: Gyula
country: Hungary
facility: Bekes Megyei Pandy Kalman Korhaz
city: Kaposvár
country: Hungary
facility: Kaposi Mór Oktató Kórház
city: Szeged
country: Hungary
facility: SZTE II. sz Belgyogyoszati Klinika es Kardiologiai Kozpont
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőint
city: Maastricht
country: Netherlands
facility: University Hospital Maastricht
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Auckland
country: New Zealand
facility: Auckland District Health Board, Auckland City Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Canterbury District Health Board
city: Takapuna
country: New Zealand
facility: North Shore Hospital
city: Wellington
country: New Zealand
facility: CCDHB - Wellington Hospital
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University
state: Republic Of Bashkortostan
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
state: Saratov Region
city: Moscow
country: Russian Federation
facility: National Haematology Research Center
city: Petrozavodsk
country: Russian Federation
facility: Republican Hopsital n.a. V.A. Baranov
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Transfusiology
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy n.a. S.M. Kirov
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: Merseyside
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
state: N. Ireland
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Hammersmith Hosp - ICH NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Sr. Director, Head of Clinical Operations
name: Simran Singh
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Verstovsek S, Mesa R, Talpaz M, Kiladjian JJ, Harrison CN, Oh ST, Vannucchi AM, Rampal R, Scott BL, Buckley SA, Craig AR, Roman-Torres K, Mascarenhas JO. Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. Haematologica. 2022 Jul 1;107(7):1599-1607. doi: 10.3324/haematol.2021.279415.
citation: Tremblay D, Mesa R, Scott B, Buckley S, Roman-Torres K, Verstovsek S, Mascarenhas J. Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden. Blood Adv. 2020 Dec 8;4(23):5929-5935. doi: 10.1182/bloodadvances.2020002970.