Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

Primary Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01773187
• Other study ID #: PERSIST-1 (PAC325)
• Status: Terminated
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: April 2016

Study information

• Verified date: September 2020
• 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 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 327
• Est. completion date: April 2016
• Est. primary completion date: January 2015
• 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)

• 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pacritinib

• Best Available Therapy

Locations

Country	Name	City	State
Australia	CTI Investigational Site 61006	Box Hill
Australia	CTI Investigational Site 61001	Coffs Harbour
Australia	CTI Investigational Site 61005	Geelong
Australia	CTI Investigational Site 61003	Gosford
Australia	CTI Investigational Site 61004	Hobart
Australia	CTI Investigational Site 61002	Milton
Belgium	CTI Investigational Site 32002	Antwerp
Belgium	CTI Investigational Site 32003	Antwerp
Belgium	CTI Investigational Site 32001	Brugge
Belgium	CTI Investigational Site 32005	Bruxelles
Belgium	CTI Investigational Site 32004	La Louviere
Czechia	CTI Investigational Site 42003	Brno
Czechia	CTI Investigational Site 42001	Olomouc
Czechia	CTI Investigational Site 42002	Plzen
Czechia	CTI Investigational Site 42004	Prague
France	CTI Investigational Site 33005	Amiens
France	CTI Investigational Site 33006	Caen
France	CTI Investigational Site 33011	Grenoble
France	CTI Investigational Site 33012	Lens
France	CTI Investigational Site 33007	Lille
France	CTI Investigational Site 33001	Nimes Cedex
France	CTI Investigational Site 33004	Paris
France	CTI Investigational Site 33008	Paris
France	CTI Investigational Site 33009	Pessac
France	CTI Investigational Site 33010	Pierre Benite
France	CTI Investigational Site 33003	Strasbourg
France	CTI Investigational Site 33002	Toulouse
Germany	CTI Investigational Site 49006	Berlin
Germany	CTI Investigational Site 49007	Berlin
Germany	CTI Investigational Site 49003	Dresden
Germany	CTI Investigational Site 49008	Essen
Germany	CTI Investigational Site 49002	Freiburg
Germany	CTI Investigational Site 49001	Koln
Germany	CTI Investigational Site 49005	Mainz
Germany	CTI Investigational Site 49004	Munchen
Germany	CTI Investigational Site 49009	Munster
Hungary	CTI Investigational Site 36002	Budapest
Hungary	CTI Investigational Site 36005	Debrecen
Hungary	CTI Investigational Site 36006	Gyula
Hungary	CTI Investigational Site 36003	Kaposvar
Hungary	CTI Investigational Site 36004	Kecskemet
Hungary	CTI Investigational Site 36001	Szeged
Hungary	CTI Investigational Site 36008	Szolnok
Hungary	CTI Investigational Site 36007	Szombathely
Italy	CTI Investigational Site 39003	Bologna
Italy	CTI Investigational Site 39001	Firenze
Italy	CTI Investigational Site 39005	Milano
Italy	CTI Investigational Site 39004	Monza
Italy	CTI Investigational Site 39002	Padova
Italy	CTI Investigational Site 39008	Reggio Emilia
Italy	CTI Investigational Site 39006	Rimini
Netherlands	CTI Investigational Site 31001	Amsterdam
Netherlands	CTI Investigational Site 31002	Maastricht
Netherlands	CTI Investigational Site 31003	Rotterdam
Netherlands	CTI Investigational Site 31004	Utrecht
New Zealand	CTI Investigational Site 64001	Christchurch
New Zealand	CTI Investigational Site 64004	Dunedin
New Zealand	CTI Investigational Site 64002	Hamilton
New Zealand	CTI Investigational Site 64003	Takapuna
Russian Federation	CTI Investigational Site 70011	Izhevsk
Russian Federation	CTI Investigational Site 70008	Moscow
Russian Federation	CTI Investigational Site 70009	Moscow
Russian Federation	CTI Investigational Site 70002	Petrozavodsk
Russian Federation	CTI Investigational Site 70010	Saint Petersburg
Russian Federation	CTI Investigational Site 70005	Samara
Russian Federation	CTI Investigational Site 70006	Sochi
Russian Federation	CTI Investigational Site 70001	St. Petersburg
Russian Federation	CTI Investigational Site 70004	St. Petersburg
Russian Federation	CTI Investigational Site 70007	Volgograd
United Kingdom	CTI Investigational Site 44004	Birmingham
United Kingdom	CTI Investigational Site 44008	Bournemouth
United Kingdom	CTI Investigational Site 44002	Cambridge
United Kingdom	CTI Investigational Site 44003	Cardiff
United Kingdom	CTI Investigational Site 44001	London
United Kingdom	CTI Investigational Site 44007	London
United Kingdom	CTI Investigational Site 44006	Manchester
United Kingdom	CTI Investigational Site 44005	Oxford
United States	CTI Investigational Site 10003	Greenville	South Carolina
United States	CTI Investigational Site 10001	Morristown	New Jersey
United States	CTI Investigational Site 10004	Omaha	Nebraska
United States	CTI Investigational Site 10002	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Countries where clinical trial is conducted

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

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spleen Volume Reduction	Number 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
Secondary	Total Symptom Score (TSS) Reduction	Number of patients with >= 50% reduction in total 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