Phase 2 Study: An Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post- Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib

NCT ID: NCT04884191

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 165 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-31
• Study Completion Date: 2019-09-04

Brief Summary

This was an open-label, randomized, dose-finding study in patients with primary or secondary MF (Dynamic International Prognostic Scoring System [DIPSS] risk score of Intermediate-1 to High-Risk) who were previously treated with ruxolitinib. The study was designed to support a pacritinib dosage selection decision with evaluation of 3 dosages.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post- Essential Thrombocythemia Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pacritinib 100 mg QD

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

Pacritinib

Pacritinib 100 mg BID

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

Pacritinib

Pacritinib 200 mg BID

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

Pacritinib

Interventions

Pacritinib

Pacritinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)

2. DIPSS Intermediate-1, Intermediate -2, or High-risk (Passamonti et al 2010)

3. Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following:

1. Treatment for ≥3 months with inadequate efficacy response defined as <10% SVR by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response; and/or

2. Treatment for ≥28 days complicated by either

i. Development of a red blood cell (RBC) transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (NCI) CTCAE grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of <20 mg BID

4. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination

5. TSS of ≥10 on the MPN-SAF TSS 2.0 or patients with a single symptom score of ≥5 or 2 symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats

6. Age ≥18 years old

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

8. Peripheral blast count of <10% throughout the Screening period

9. Absolute neutrophil count of >500/μL

10. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase [SGPT]), ≤3 × the 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

11. Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN

12. Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan

13. If fertile, willing to use effective birth control methods during the study

14. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study

15. Able to understand and willing to complete symptom assessments using a PRO instrument

16. Provision of informed consent

Exclusion Criteria

1. Life expectancy <6 months

2. Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete allo-SCT

3. History of splenectomy or planning to undergo splenectomy

4. Splenic irradiation within the last 6 months

5. Previously treated with pacritinib

6. Patients receiving high-dose ruxolitinib (more than 10 mg BID or 20 mg QD) who cannot tolerate tapering down ruxolitinib to 10 mg BID or less prior to the first dose of pacritinib

7. Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ≤100 mg per day, within the last 2 weeks

8. Treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 inducer within the last 2 weeks

9. Treatment with medications that can prolong the QTc interval within the last 2 weeks

10. Treatment with an experimental therapy within the last 28 days

11. Significant recent bleeding history defined as NCI CTCAE grade ≥2 within the last 3 months, unless precipitated by an inciting event (eg, surgery, trauma, or injury)

12. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety.

13. New York Heart Association Class II, III, or IV congestive heart failure

14. Any history of CTCAE grade ≥2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the medical monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.

15. QTc prolongation >450 ms based on the mean of triplicate ECGs or other factors 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], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)

16. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication

17. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or constipation

18. 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 nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma

19. 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

20. Known seropositivity for human immunodeficiency virus

21. Known active hepatitis A, B, or C virus infection

22. Women who are pregnant or lactating

23. Concurrent enrollment in another interventional trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CTI BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Hospital

Phoenix, Arizona, United States

City of Hope

Duarte, California, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Stanford Cancer Institute

Stanford, California, United States

Yale School of Medicine

New Haven, Connecticut, United States

Medical Faculty Associates, Inc.

Washington D.C., District of Columbia, United States

Florida Cancer Specialists & Research Institute

Fort Myers, Florida, United States

Florida Cancer Specialists & Research Institute

St. Petersburg, Florida, United States

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

Saint Agnes Hospital

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Weill Cornell Medical College

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Columbia University

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Duke University Hospital

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Tennessee Oncology

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Texas Health Science Center at San Antonio School of Medicine

San Antonio, Texas, United States

University of Utah School of Medicine

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

CHU Hopital Sud

Amiens, , France

Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez

Lille, , France

CHU de Nimes - Hopital Universitaire Caremeau

Nîmes, , France

Hôpital Saint-Louis

Paris, , France

CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Centre Hospitalier Lyon-Sud

Pierre-Bénite, , France

Centre Hospitalier Universitaire de Toulouse- Hôpital Purpan

Toulouse, , France

SE AOK I. sx. Belgyogyaszati Klinika

Budapest, , Hungary

Debreceni Egyetem Klinikai Központ

Debrecen, , Hungary

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, , Hungary

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura Dei Tumori

Meldola, , Italy

ASST Monza - Ospedale San Gerardo

Monza, , Italy

Yeungnam University Medical Center

Daegu, , South Korea

Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Hospital del Mar

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Clínica Universidad de Navarra

Pamplona, , Spain

Skane University Hospital Lund

Lund, , Sweden

Orebro University Hospital

Örebro, , Sweden

Beatson West of Scotland Cancer Center

Glasgow, , United Kingdom

Barts Health NHS Trust - The Royal London Hospital

London, , United Kingdom

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, , United Kingdom

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, , United Kingdom

Countries

United States; France; Hungary; Italy; South Korea; Spain; Sweden; United Kingdom

References

Verstovsek S, Mesa R, Talpaz M, Kiladjian JJ, Harrison CN, Oh ST, Vannucchi AM, Rampal R, Scott BL, Buckley SA, Craig AR, Roman-Torres K, Mascarenhas JO. Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. Haematologica. 2022 Jul 1;107(7):1599-1607. doi: 10.3324/haematol.2021.279415.

Reference Type: DERIVED

PMID: 34551507 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PAC203

Identifier Type: -

Identifier Source: org_study_id