Clinical trial NCT01773187: Pacritinib Versus Best Available Therapy to Treat Myelofibrosis
Official title: A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With 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 Disease
Splenomegaly
Pacritinib
MPN-SAF
MPN-SAF TSS
Anemia
Myeloproliferative Neoplasm
Spleen volume
Thrombocytopenia
SB1518
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2013-01-23
Enrollment: 327
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 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 primary or secondary myelofibrosis. Approximately 322 eligible patients will be randomized in a 2:1 allocation to pacritinib (400mg QD) or BAT (includes any physician-selected treatment for myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)). 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)
* 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
* No spleen radiation therapy for 6-12 months
* Last therapy for myelofibrosis was 2-4 weeks ago, including any erythropoietic or thrombopoietic agent
* Not pregnant, not lactating, and agree to use effective birth control

Exclusion Criteria:

* Prior treatment with a JAK2 inhibitor
* 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
* 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
Secondary outcomes:
measure: Total Symptom Score (TSS) Reduction
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CTI Investigational Site 10002
state: Arizona
city: Omaha
country: United States
facility: CTI Investigational Site 10004
state: Nebraska
city: Morristown
country: United States
facility: CTI Investigational Site 10001
state: New Jersey
city: Greenville
country: United States
facility: CTI Investigational Site 10003
state: South Carolina
city: Box Hill
country: Australia
facility: CTI Investigational Site 61006
city: Coffs Harbour
country: Australia
facility: CTI Investigational Site 61001
city: Geelong
country: Australia
facility: CTI Investigational Site 61005
city: Gosford
country: Australia
facility: CTI Investigational Site 61003
city: Hobart
country: Australia
facility: CTI Investigational Site 61004
city: Milton
country: Australia
facility: CTI Investigational Site 61002
city: Antwerp
country: Belgium
facility: CTI Investigational Site 32002
city: Antwerp
country: Belgium
facility: CTI Investigational Site 32003
city: Brugge
country: Belgium
facility: CTI Investigational Site 32001
city: Bruxelles
country: Belgium
facility: CTI Investigational Site 32005
city: La Louviere
country: Belgium
facility: CTI Investigational Site 32004
city: Brno
country: Czechia
facility: CTI Investigational Site 42003
city: Olomouc
country: Czechia
facility: CTI Investigational Site 42001
city: Plzen
country: Czechia
facility: CTI Investigational Site 42002
city: Prague
country: Czechia
facility: CTI Investigational Site 42004
city: Amiens
country: France
facility: CTI Investigational Site 33005
city: Caen
country: France
facility: CTI Investigational Site 33006
city: Grenoble
country: France
facility: CTI Investigational Site 33011
city: Lens
country: France
facility: CTI Investigational Site 33012
city: Lille
country: France
facility: CTI Investigational Site 33007
city: Nimes Cedex
country: France
facility: CTI Investigational Site 33001
city: Paris
country: France
facility: CTI Investigational Site 33004
city: Paris
country: France
facility: CTI Investigational Site 33008
city: Pessac
country: France
facility: CTI Investigational Site 33009
city: Pierre Benite
country: France
facility: CTI Investigational Site 33010
city: Strasbourg
country: France
facility: CTI Investigational Site 33003
city: Toulouse
country: France
facility: CTI Investigational Site 33002
city: Berlin
country: Germany
facility: CTI Investigational Site 49006
city: Berlin
country: Germany
facility: CTI Investigational Site 49007
city: Dresden
country: Germany
facility: CTI Investigational Site 49003
city: Essen
country: Germany
facility: CTI Investigational Site 49008
city: Freiburg
country: Germany
facility: CTI Investigational Site 49002
city: Koln
country: Germany
facility: CTI Investigational Site 49001
city: Mainz
country: Germany
facility: CTI Investigational Site 49005
city: Munchen
country: Germany
facility: CTI Investigational Site 49004
city: Munster
country: Germany
facility: CTI Investigational Site 49009
city: Budapest
country: Hungary
facility: CTI Investigational Site 36002
city: Debrecen
country: Hungary
facility: CTI Investigational Site 36005
city: Gyula
country: Hungary
facility: CTI Investigational Site 36006
city: Kaposvar
country: Hungary
facility: CTI Investigational Site 36003
city: Kecskemet
country: Hungary
facility: CTI Investigational Site 36004
city: Szeged
country: Hungary
facility: CTI Investigational Site 36001
city: Szolnok
country: Hungary
facility: CTI Investigational Site 36008
city: Szombathely
country: Hungary
facility: CTI Investigational Site 36007
city: Bologna
country: Italy
facility: CTI Investigational Site 39003
city: Firenze
country: Italy
facility: CTI Investigational Site 39001
city: Milano
country: Italy
facility: CTI Investigational Site 39005
city: Monza
country: Italy
facility: CTI Investigational Site 39004
city: Padova
country: Italy
facility: CTI Investigational Site 39002
city: Reggio Emilia
country: Italy
facility: CTI Investigational Site 39008
city: Rimini
country: Italy
facility: CTI Investigational Site 39006
city: Amsterdam
country: Netherlands
facility: CTI Investigational Site 31001
city: Maastricht
country: Netherlands
facility: CTI Investigational Site 31002
city: Rotterdam
country: Netherlands
facility: CTI Investigational Site 31003
city: Utrecht
country: Netherlands
facility: CTI Investigational Site 31004
city: Christchurch
country: New Zealand
facility: CTI Investigational Site 64001
city: Dunedin
country: New Zealand
facility: CTI Investigational Site 64004
city: Hamilton
country: New Zealand
facility: CTI Investigational Site 64002
city: Takapuna
country: New Zealand
facility: CTI Investigational Site 64003
city: Izhevsk
country: Russian Federation
facility: CTI Investigational Site 70011
city: Moscow
country: Russian Federation
facility: CTI Investigational Site 70008
city: Moscow
country: Russian Federation
facility: CTI Investigational Site 70009
city: Petrozavodsk
country: Russian Federation
facility: CTI Investigational Site 70002
city: Saint Petersburg
country: Russian Federation
facility: CTI Investigational Site 70010
city: Samara
country: Russian Federation
facility: CTI Investigational Site 70005
city: Sochi
country: Russian Federation
facility: CTI Investigational Site 70006
city: St. Petersburg
country: Russian Federation
facility: CTI Investigational Site 70001
city: St. Petersburg
country: Russian Federation
facility: CTI Investigational Site 70004
city: Volgograd
country: Russian Federation
facility: CTI Investigational Site 70007
city: Birmingham
country: United Kingdom
facility: CTI Investigational Site 44004
city: Bournemouth
country: United Kingdom
facility: CTI Investigational Site 44008
city: Cambridge
country: United Kingdom
facility: CTI Investigational Site 44002
city: Cardiff
country: United Kingdom
facility: CTI Investigational Site 44003
city: London
country: United Kingdom
facility: CTI Investigational Site 44001
city: London
country: United Kingdom
facility: CTI Investigational Site 44007
city: Manchester
country: United Kingdom
facility: CTI Investigational Site 44006
city: Oxford
country: United Kingdom
facility: CTI Investigational Site 44005
Study officials:
affiliation: VP, Pharmacovigilance, Clinical Operations, QA
name: Beth Ziemba
role: STUDY_DIRECTOR
References:
citation: Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, Perkins A, Prasad R, Mayer J, Demeter J, Ganly P, Singer JW, Zhou H, Dean JP, Te Boekhorst PA, Nangalia J, Kiladjian JJ, Harrison CN. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-e236. doi: 10.1016/S2352-3026(17)30027-3. Epub 2017 Mar 20.
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.