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Withdrawn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
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
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
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
NCT ID
NCT02584777
First Posted
October 21, 2015
Last Updated
May 3, 2021
Sponsor
Baxalta now part of Shire
Collaborators
CTI BioPharma
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
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