search
Back to results

A Phase II Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Myelofibrosis

Primary Purpose

Primary Myelofibrosis

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pacritinib
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Myelofibrosis focused on measuring Post-essential thrombocythemia myelofibrosis, Post-Polycythemia Vera Myelofibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Intermediate-1, intermediate-2, or high-risk PMF, PPV-MF or PET-MF as based on The Dynamic International Prognostic Scoring System (DIPSS) criteria
  2. Palpable splenomegaly ≥5 cm below the LCM in midclavicular line by physical examination
  3. TSS ≥13 on the MPN-SAF TSS 2.0, not including the inactivity question, based on a single assessment during screening visit
  4. Age ≥18 years old at the time of screening (or minimum age of legal consent consistent with local regulations, if minimum is >18 years of age)
  5. ECOG performance status 0 to 3
  6. Peripheral blast count <10%
  7. Absolute neutrophil count >500/μL
  8. Participants who are platelet or RBC transfusion dependent are eligible
  9. Adequate liver and renal function, defined by liver transaminases (AST/serum glutamic oxaloacetic transaminase [SOOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) ≤3 × upper limit of normal ([ULN], AST/ALT ≤5 × ULN if transaminase elevation is related to MF), direct bilirubin ≤4 × ULN, and creatinine ≤2.5 mg/dL
  10. At least 6 months from prior splenic irradiation
  11. At least 12 months from prior 32P therapy
  12. At least 1 week since prior treatment (most recent dose) with a potent CYP3A4 inhibitor or inducer
  13. At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF
  14. At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF
  15. If fertile, both males and females must agree to use effective birth control.
  16. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument and comply with treatment and study procedures of the protocol
  17. Able to understand and willing to sign the informed consent form (ICF)
  18. Participant is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

  1. Any GI or metabolic condition that could interfere with absorption of oral medication
  2. Life expectancy <6 months
  3. Prior treatment with a JAK2 inhibitor
  4. Completed ASCT, or are eligible for and willing to complete ASCT
  5. History of splenectomy or planning to undergo splenectomy
  6. Uncontrolled intercurrent illness, including but not limited to ongoing active infection, or psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements
  7. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ confined, or treated non-metastatic prostate cancer with negative prostate specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
  8. Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or constipation
  9. Clinically symptomatic and uncontrolled cardiovascular disease
  10. History of any of the following within 6 months prior to first dose of pacritinib: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure
  11. New York Heart Association Class II, III, or IV congestive heart failure
  12. Participants with NCI CTCAE (version 4.03) Grade 2 cardiac arrhythmias may be considered for inclusion, with the approval of the medical monitor, if the arrhythmias are stable, asymptomatic and unlikely to affect participant safety. Participants will be excluded if they have ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥3, QTc prolongation >450 ms, or other conditions that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
  13. Erythropoietic agent within 28 days prior to first dose of pacritinib
  14. Thrombopoietic agent within 14 days prior to first dose of pacritinib
  15. Known seropositivity for human immunodeficiency virus or syphilis, or known active hepatitis A, B or C virus infection
  16. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
  17. Participant is a family member or employee of the investigator
  18. If female, participant is pregnant or breastfeeding at the time of enrollment. Even if breastfeeding can be discontinued, the participant should not be enrolled in the study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Pacritinib

    Arm Description

    Oral administration

    Outcomes

    Primary Outcome Measures

    Proportion of participants achieving a ≥35% reduction in spleen volume
    Measured by MRI or CT scan

    Secondary Outcome Measures

    Proportion of participants with ≥50% reduction in total symptom score (TSS)
    Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) TSS 2.0
    Proportion of participants with baseline platelet count <100,000/μL achieving ≥35% reduction in spleen volume
    Measured by MRI or CT scan
    Proportion of participants with baseline platelet count <100,000/μL achieving ≥50% reduction in total symptom score (TSS)
    Proportion of participants with baseline platelet count <50,000/μL achieving ≥35% reduction in spleen volume
    Measured by MRI or CT scan
    Proportion of participants with baseline platelet count <50,000/μL achieving ≥50% reduction in total symptom score (TSS)
    Clinically significant adverse events (AEs)
    Clinically significant changes in laboratory results
    Clinically significant changes in vital signs
    Clinically significant changes in electrocardiograms (ECGs)
    Pacritinib pharmacokinetic (PK) parameter: maximum observed concentration (Cmax)
    Pacritinib pharmacokinetic (PK) parameter: Time of maximum observed concentration (Tmax)
    Pacritinib pharmacokinetic (PK) parameter: minimum observed concentration (Cmin)
    Pacritinib pharmacokinetic (PK) parameter: area under the concentration curve (AUC)
    Pacritinib pharmacokinetic (PK) parameter: apparent volume of distribution (V/F)
    Pharmacodynamic parameter: Maximum observed effect (Emax)
    Pharmacodynamic parameter: time of maximum observed effect (tEmax)
    Pharmacodynamic parameter: area under the effect curve (AUEC)

    Full Information

    First Posted
    October 21, 2015
    Last Updated
    May 3, 2021
    Sponsor
    Baxalta now part of Shire
    Collaborators
    CTI BioPharma
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02584777
    Brief Title
    A Phase II Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Myelofibrosis
    Official Title
    A Phase II, Prospective, Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Asian Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post- Essential Thrombocythemia Myelofibrosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2021
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    November 30, 2015 (Actual)
    Primary Completion Date
    September 30, 2017 (Actual)
    Study Completion Date
    August 31, 2020 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Baxalta now part of Shire
    Collaborators
    CTI BioPharma

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    To evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of pacritinib in Asian subjects with myelofibrosis (MF), which includes primary MF (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Myelofibrosis
    Keywords
    Post-essential thrombocythemia myelofibrosis, Post-Polycythemia Vera Myelofibrosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Pacritinib
    Arm Type
    Experimental
    Arm Description
    Oral administration
    Intervention Type
    Biological
    Intervention Name(s)
    Pacritinib
    Intervention Description
    QD (Once a day)
    Primary Outcome Measure Information:
    Title
    Proportion of participants achieving a ≥35% reduction in spleen volume
    Description
    Measured by MRI or CT scan
    Time Frame
    Baseline to Week 24
    Secondary Outcome Measure Information:
    Title
    Proportion of participants with ≥50% reduction in total symptom score (TSS)
    Description
    Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) TSS 2.0
    Time Frame
    Baseline to Week 24
    Title
    Proportion of participants with baseline platelet count <100,000/μL achieving ≥35% reduction in spleen volume
    Description
    Measured by MRI or CT scan
    Time Frame
    Baseline to Week 24
    Title
    Proportion of participants with baseline platelet count <100,000/μL achieving ≥50% reduction in total symptom score (TSS)
    Time Frame
    Baseline to Week 24
    Title
    Proportion of participants with baseline platelet count <50,000/μL achieving ≥35% reduction in spleen volume
    Description
    Measured by MRI or CT scan
    Time Frame
    Baseline to Week 24
    Title
    Proportion of participants with baseline platelet count <50,000/μL achieving ≥50% reduction in total symptom score (TSS)
    Time Frame
    Baseline to Week 24
    Title
    Clinically significant adverse events (AEs)
    Time Frame
    Throughout the study period of approximately 5 years
    Title
    Clinically significant changes in laboratory results
    Time Frame
    Throughout the study period of approximately 5 years
    Title
    Clinically significant changes in vital signs
    Time Frame
    Throughout the study period of approximately 5 years
    Title
    Clinically significant changes in electrocardiograms (ECGs)
    Time Frame
    Throughout the study period of approximately 5 years
    Title
    Pacritinib pharmacokinetic (PK) parameter: maximum observed concentration (Cmax)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pacritinib pharmacokinetic (PK) parameter: Time of maximum observed concentration (Tmax)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pacritinib pharmacokinetic (PK) parameter: minimum observed concentration (Cmin)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pacritinib pharmacokinetic (PK) parameter: area under the concentration curve (AUC)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pacritinib pharmacokinetic (PK) parameter: apparent volume of distribution (V/F)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pharmacodynamic parameter: Maximum observed effect (Emax)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pharmacodynamic parameter: time of maximum observed effect (tEmax)
    Time Frame
    Baseline; weeks 3, 12 & 24
    Title
    Pharmacodynamic parameter: area under the effect curve (AUEC)
    Time Frame
    Baseline; weeks 3, 12 & 24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Intermediate-1, intermediate-2, or high-risk PMF, PPV-MF or PET-MF as based on The Dynamic International Prognostic Scoring System (DIPSS) criteria Palpable splenomegaly ≥5 cm below the LCM in midclavicular line by physical examination TSS ≥13 on the MPN-SAF TSS 2.0, not including the inactivity question, based on a single assessment during screening visit Age ≥18 years old at the time of screening (or minimum age of legal consent consistent with local regulations, if minimum is >18 years of age) ECOG performance status 0 to 3 Peripheral blast count <10% Absolute neutrophil count >500/μL Participants who are platelet or RBC transfusion dependent are eligible Adequate liver and renal function, defined by liver transaminases (AST/serum glutamic oxaloacetic transaminase [SOOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) ≤3 × upper limit of normal ([ULN], AST/ALT ≤5 × ULN if transaminase elevation is related to MF), direct bilirubin ≤4 × ULN, and creatinine ≤2.5 mg/dL At least 6 months from prior splenic irradiation At least 12 months from prior 32P therapy At least 1 week since prior treatment (most recent dose) with a potent CYP3A4 inhibitor or inducer At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF If fertile, both males and females must agree to use effective birth control. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument and comply with treatment and study procedures of the protocol Able to understand and willing to sign the informed consent form (ICF) Participant is willing and able to comply with the requirements of the protocol Exclusion Criteria: Any GI or metabolic condition that could interfere with absorption of oral medication Life expectancy <6 months Prior treatment with a JAK2 inhibitor Completed ASCT, or are eligible for and willing to complete ASCT History of splenectomy or planning to undergo splenectomy Uncontrolled intercurrent illness, including but not limited to ongoing active infection, or psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ confined, or treated non-metastatic prostate cancer with negative prostate specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or constipation Clinically symptomatic and uncontrolled cardiovascular disease History of any of the following within 6 months prior to first dose of pacritinib: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure New York Heart Association Class II, III, or IV congestive heart failure Participants with NCI CTCAE (version 4.03) Grade 2 cardiac arrhythmias may be considered for inclusion, with the approval of the medical monitor, if the arrhythmias are stable, asymptomatic and unlikely to affect participant safety. Participants will be excluded if they have ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥3, QTc prolongation >450 ms, or other conditions that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome) Erythropoietic agent within 28 days prior to first dose of pacritinib Thrombopoietic agent within 14 days prior to first dose of pacritinib Known seropositivity for human immunodeficiency virus or syphilis, or known active hepatitis A, B or C virus infection Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study Participant is a family member or employee of the investigator If female, participant is pregnant or breastfeeding at the time of enrollment. Even if breastfeeding can be discontinued, the participant should not be enrolled in the study
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Study Director
    Organizational Affiliation
    Takeda
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    A Phase II Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Myelofibrosis

    We'll reach out to this number within 24 hrs