Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

Phase 3

Terminated

• Conditions: Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Primary Myelofibrosis
• Interventions: Drug: Pacritinib; Drug: Best Available Therapy

• Registration Number: NCT01773187
• Lead Sponsor: CTI BioPharma

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.

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-01-18
• Study First Submitted QC: 2013-01-18
• Study First Posted: 2013-01-23
• Primary Completion: 2015-01
• Study Completion: 2016-04
• Results First Submitted: 2018-12-11
• Status Verified: 2020-09
• Results First Submitted QC: 2020-09-25
• Last Update Submitted: 2020-09-25
• Results First Posted: 2020-09-29
• Last Update Posted: 2020-09-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 327

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pacritinib	Pacritinib	Pacritinib 400 mg QD
Best Available Therapy	Best Available Therapy	BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)

Primary Outcome Measures

Name	Time	Method
Spleen Volume Reduction	Baseline to Week 24	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)

Secondary Outcome Measures

Name	Time	Method
Total Symptom Score (TSS) Reduction	Baseline to Week 24	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.

Trial Locations

Locations (81)

CTI Investigational Site 10004; 🇺🇸 Omaha, Nebraska, United States

CTI Investigational Site 10002; 🇺🇸 Scottsdale, Arizona, United States

CTI Investigational Site 61006; 🇦🇺 Box Hill, Australia

CTI Investigational Site 10003; 🇺🇸 Greenville, South Carolina, United States

CTI Investigational Site 61005; 🇦🇺 Geelong, Australia

CTI Investigational Site 61003; 🇦🇺 Gosford, Australia

CTI Investigational Site 61004; 🇦🇺 Hobart, Australia

CTI Investigational Site 61002; 🇦🇺 Milton, Australia

CTI Investigational Site 32002; 🇧🇪 Antwerp, Belgium

CTI Investigational Site 32003; 🇧🇪 Antwerp, Belgium

CTI Investigational Site 32005; 🇧🇪 Bruxelles, Belgium

CTI Investigational Site 42003; 🇨🇿 Brno, Czechia

CTI Investigational Site 32004; 🇧🇪 La Louviere, Belgium

CTI Investigational Site 42002; 🇨🇿 Plzen, Czechia

CTI Investigational Site 42001; 🇨🇿 Olomouc, Czechia

CTI Investigational Site 42004; 🇨🇿 Prague, Czechia

CTI Investigational Site 33003; 🇫🇷 Strasbourg, France

CTI Investigational Site 33005; 🇫🇷 Amiens, France

CTI Investigational Site 33006; 🇫🇷 Caen, France

CTI Investigational Site 33007; 🇫🇷 Lille, France

CTI Investigational Site 33011; 🇫🇷 Grenoble, France

CTI Investigational Site 33012; 🇫🇷 Lens, 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 49003; 🇩🇪 Dresden, Germany

CTI Investigational Site 49007; 🇩🇪 Berlin, Germany

CTI Investigational Site 49006; 🇩🇪 Berlin, Germany

CTI Investigational Site 49008; 🇩🇪 Essen, Germany

CTI Investigational Site 49002; 🇩🇪 Freiburg, Germany

CTI Investigational Site 49001; 🇩🇪 Koln, Germany

CTI Investigational Site 49009; 🇩🇪 Munster, Germany

CTI Investigational Site 49004; 🇩🇪 Munchen, Germany

CTI Investigational Site 49005; 🇩🇪 Mainz, Germany

CTI Investigational Site 36002; 🇭🇺 Budapest, Hungary

CTI Investigational Site 36006; 🇭🇺 Gyula, Hungary

CTI Investigational Site 36004; 🇭🇺 Kecskemet, Hungary

CTI Investigational Site 36008; 🇭🇺 Szolnok, Hungary

CTI Investigational Site 39001; 🇮🇹 Firenze, Italy

CTI Investigational Site 39003; 🇮🇹 Bologna, Italy

CTI Investigational Site 39004; 🇮🇹 Monza, Italy

CTI Investigational Site 31002; 🇳🇱 Maastricht, Netherlands

CTI Investigational Site 31003; 🇳🇱 Rotterdam, Netherlands

CTI Investigational Site 31004; 🇳🇱 Utrecht, Netherlands

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, New Zealand

CTI Investigational Site 70008; 🇷🇺 Moscow, Russian Federation

CTI Investigational Site 70009; 🇷🇺 Moscow, Russian Federation

CTI Investigational Site 70010; 🇷🇺 Saint Petersburg, Russian Federation

CTI Investigational Site 70005; 🇷🇺 Samara, Russian Federation

CTI Investigational Site 70007; 🇷🇺 Volgograd, Russian Federation

CTI Investigational Site 70001; 🇷🇺 St. Petersburg, Russian Federation

CTI Investigational Site 44004; 🇬🇧 Birmingham, United Kingdom

CTI Investigational Site 44002; 🇬🇧 Cambridge, United Kingdom

CTI Investigational Site 44008; 🇬🇧 Bournemouth, 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 Kingdom

CTI Investigational Site 61001; 🇦🇺 Coffs Harbour, Australia

CTI Investigational Site 70002; 🇷🇺 Petrozavodsk, Russian Federation

CTI Investigational Site 70006; 🇷🇺 Sochi, Russian Federation

CTI Investigational Site 39005; 🇮🇹 Milano, Italy

CTI Investigational Site 39002; 🇮🇹 Padova, Italy

CTI Investigational Site 39008; 🇮🇹 Reggio Emilia, Italy

CTI Investigational Site 39006; 🇮🇹 Rimini, Italy

CTI Investigational Site 33002; 🇫🇷 Toulouse, France

CTI Investigational Site 70011; 🇷🇺 Izhevsk, Russian Federation

CTI Investigational Site 32001; 🇧🇪 Brugge, Belgium

CTI Investigational Site 36007; 🇭🇺 Szombathely, Hungary

CTI Investigational Site 36003; 🇭🇺 Kaposvar, Hungary

CTI Investigational Site 36001; 🇭🇺 Szeged, Hungary

CTI Investigational Site 31001; 🇳🇱 Amsterdam, Netherlands

CTI Investigational Site 10001; 🇺🇸 Morristown, New Jersey, United States

CTI Investigational Site 36005; 🇭🇺 Debrecen, Hungary

CTI Investigational Site 70004; 🇷🇺 St. Petersburg, Russian Federation