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Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia (PAC326)

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ClinicalTrials.gov Identifier: NCT02055781
Recruitment Status : Terminated
First Posted : February 5, 2014
Last Update Posted : October 22, 2018
Sponsor:
Information provided by (Responsible Party):
CTI BioPharma

Tracking Information
First Submitted Date  ICMJE February 3, 2014
First Posted Date  ICMJE February 5, 2014
Last Update Posted Date October 22, 2018
Study Start Date  ICMJE December 2013
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy in patients with thrombocytopenia and primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis; 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) and the proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Original Primary Outcome Measures  ICMJE
 (submitted: February 4, 2014)
Efficacy [ Time Frame: Baseline to Week 24 ]
To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy in patients with thrombocytopenia and primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis; 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) and the proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Change History Complete list of historical versions of study NCT02055781 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • To compare the efficacy of once-daily pacritinib with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
    To compare the efficacy of once-daily pacritinib with that of Best Available Therapy, as assessed by 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) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
  • To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
    To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy, as assessed by 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) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2014)
  • Efficacy [ Time Frame: Baseline to Week 24 ]
    To compare the efficacy of once-daily pacritinib with that of Best Available Therapy, as assessed by 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) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
  • Efficacy [ Time Frame: Baseline to Week 24 ]
    To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy, as assessed by 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) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia
Official Title  ICMJE 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
Brief Summary The primary hypothesis of the study is that treatment with either once-daily or twice-daily pacritinib results in a greater proportion of patients with thrombocytopenia and myelofibrosis achieving ≥ 35% reduction in spleen volume from baseline to Week 24 than treatment with Best Available Therapy, and a greater proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Detailed Description The primary objective is to compare the efficacy of two dose-schedule arms(s) of pacritinib (pooled once-daily [QD] and twice-daily [BID] dosing arms) with that of best available therapy (BAT) in patients with thrombocytopenia and primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF). The efficacy co-endpoints for this analysis are the proportion 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) scan and the proportion of patients achieving a ≥ 50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis
  • Post-polycythemia Vera Myelofibrosis
  • Post-essential Thrombocythemia Myelofibrosis
Intervention  ICMJE
  • Drug: Pacritinib
  • Drug: Best Available Therapy
Study Arms  ICMJE
  • Experimental: Pacritinib, Once Daily
    Pacritinib 400 mg taken orally, once daily
    Intervention: Drug: Pacritinib
  • Experimental: Pacritinib, Twice Daily
    Pacritinib 200 mg taken orally, twice daily
    Intervention: Drug: Pacritinib
  • Active Comparator: Best Available Therapy
    Best Available Therapy includes any physician-selected treatment for primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis, such as approved JAK2 inhibitors, and may include any treatment received before study entry. Best Available Therapy may include ruxolitinib, other approved JAK2 inhibitors, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan, or other agents and may also include no treatment and symptom-directed treatment without myelofibrosis-specific treatment.
    Intervention: Drug: Best Available Therapy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 18, 2018)
311
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2014)
300
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Czechia,   France,   Germany,   Hungary,   Netherlands,   New Zealand,   Russian Federation,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02055781
Other Study ID Numbers  ICMJE PERSIST-2 (PAC326)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CTI BioPharma
Study Sponsor  ICMJE CTI BioPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mary Campbell, MD CTI BioPharma
PRS Account CTI BioPharma
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP