Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

• ClinicalTrials.gov Identifier: NCT01773187
• Recruitment Status: Terminated
• First Posted: January 23, 2013
• Results First Posted: September 29, 2020
• Last Update Posted: September 29, 2020
• Sponsor: CTI BioPharma
• Information provided by (Responsible Party): CTI BioPharma

Tracking Information

• First Submitted Date: January 18, 2013
• First Posted Date: January 23, 2013
• Results First Submitted Date: December 11, 2018
• Results First Posted Date: September 29, 2020
• Last Update Posted Date: September 29, 2020
• Actual Study Start Date: January 2013
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 25, 2020)

Spleen Volume Reduction [ Time Frame: 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)

Original Primary Outcome Measures (submitted: January 18, 2013)

Efficacy [ Time Frame: Baseline to Week 24 ]

To compare the efficacy of pacritinib with that of best available therapy (BAT) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF); the efficacy measure for this analysis is the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 by magnetic resonance imaging (MRI) or computed tomography (CT)

Current Secondary Outcome Measures (submitted: September 25, 2020)

Total Symptom Score (TSS) Reduction [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: January 18, 2013)

Symptomatic Efficacy [ Time Frame: Baseline to Week 24 ]

To compare pacritinib with best available therapy with respect to the proportion of patients with >= 50% reduction in total score from baseline to week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Primary Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Post-essential Thrombocythemia Myelofibrosis

Intervention

• Drug: Pacritinib
• Drug: Best Available Therapy

Study Arms

• Experimental: Pacritinib
  Pacritinib 400 mg QD
  Intervention: Drug: Pacritinib
• Active Comparator: Best Available Therapy
  BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)
  Intervention: Drug: Best Available Therapy

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 26, 2016): 327
• Original Estimated Enrollment (submitted: January 18, 2013): 270
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Czechia, France, Germany, Hungary, Italy, Netherlands, New Zealand, Russian Federation, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01773187
• Other Study ID Numbers: PERSIST-1 (PAC325)
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: CTI BioPharma
• Study Sponsor: CTI BioPharma
• Collaborators: Not Provided

Investigators

• Study Director: Beth Ziemba; VP, Pharmacovigilance, Clinical Operations, QA

• PRS Account: CTI BioPharma
• Verification Date: September 2020