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

May 3, 2021 updated by: Baxalta now part of Shire

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Pacritinib
Oral administration
Biological: Pacritinib
QD (Once a day)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of participants achieving a ≥35% reduction in spleen volume
Time Frame: Baseline to Week 24
Measured by MRI or CT scan
Baseline to Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of participants with ≥50% reduction in total symptom score (TSS)
Time Frame: Baseline to Week 24
Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) TSS 2.0
Baseline to Week 24
Proportion of participants with baseline platelet count <100,000/μL achieving ≥35% reduction in spleen volume
Time Frame: Baseline to Week 24
Measured by MRI or CT scan
Baseline to Week 24
Proportion of participants with baseline platelet count <100,000/μL achieving ≥50% reduction in total symptom score (TSS)
Time Frame: Baseline to Week 24
Baseline to Week 24
Proportion of participants with baseline platelet count <50,000/μL achieving ≥35% reduction in spleen volume
Time Frame: Baseline to Week 24
Measured by MRI or CT scan
Baseline to Week 24
Proportion of participants with baseline platelet count <50,000/μL achieving ≥50% reduction in total symptom score (TSS)
Time Frame: Baseline to Week 24
Baseline to Week 24
Clinically significant adverse events (AEs)
Time Frame: Throughout the study period of approximately 5 years
Throughout the study period of approximately 5 years
Clinically significant changes in laboratory results
Time Frame: Throughout the study period of approximately 5 years
Throughout the study period of approximately 5 years
Clinically significant changes in vital signs
Time Frame: Throughout the study period of approximately 5 years
Throughout the study period of approximately 5 years
Clinically significant changes in electrocardiograms (ECGs)
Time Frame: Throughout the study period of approximately 5 years
Throughout the study period of approximately 5 years
Pacritinib pharmacokinetic (PK) parameter: maximum observed concentration (Cmax)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pacritinib pharmacokinetic (PK) parameter: Time of maximum observed concentration (Tmax)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pacritinib pharmacokinetic (PK) parameter: minimum observed concentration (Cmin)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pacritinib pharmacokinetic (PK) parameter: area under the concentration curve (AUC)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pacritinib pharmacokinetic (PK) parameter: apparent volume of distribution (V/F)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pharmacodynamic parameter: Maximum observed effect (Emax)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pharmacodynamic parameter: time of maximum observed effect (tEmax)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24
Pharmacodynamic parameter: area under the effect curve (AUEC)
Time Frame: Baseline; weeks 3, 12 & 24
Baseline; weeks 3, 12 & 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Baxalta now part of Shire

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
CTI BioPharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 23, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 381401

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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