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

NCT02584777 | Withdrawn Phase 2 DMC

• 1 other identifier: 381401
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Primary Myelofibrosis

Keywords

Post-essential thrombocythemia myelofibrosis; Post-Polycythemia Vera Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving a ≥35% reduction in spleen volume

  Measured by MRI or CT scan

  Baseline to Week 24

Secondary Outcomes (17)

• Proportion of participants with ≥50% reduction in total symptom score (TSS)

  Baseline to Week 24

• Proportion of participants with baseline platelet count <100,000/μL achieving ≥35% reduction in spleen volume

  Baseline to Week 24

• Proportion of participants with baseline platelet count <100,000/μL achieving ≥50% reduction in total symptom score (TSS)

  Baseline to Week 24

• Proportion of participants with baseline platelet count <50,000/μL achieving ≥35% reduction in spleen volume

  Baseline to Week 24

• Proportion of participants with baseline platelet count <50,000/μL achieving ≥50% reduction in total symptom score (TSS)

  Baseline to Week 24

Study Arms (1)

Pacritinib

EXPERIMENTAL

Oral administration

Biological: Pacritinib

Interventions

Pacritinib BIOLOGICAL

QD (Once a day)

Pacritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• CTI BioPharma: collaborator

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 23, 2015
• Study Start: November 30, 2015
• Primary Completion: September 30, 2017
• Study Completion: August 31, 2020
• Last Updated: May 5, 2021

Record last verified: 2021-05