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

NCT04884191 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PAC203
• Study Type: interventional
• Target: 165
• Locations: 8 countries
• Sites: 62

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

Outcome Measures

Primary Outcomes (4)

• Spleen Volume Reduction Response (≥ 35%)

  Number of patients achieving a ≥ 35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans

  From Baseline to Weeks 12 and 24

• Percent Change in Spleen Volume

  Percent change from baseline

  From Baseline to Weeks 12 and 24

• Total Symptom Score Analysis

  Proportion of patients with ≥ 50% reduction in Total Symptom Score from baseline as assessed by the validated PRO instrument MPN-SAF TSS 2.0

  From Baseline to Weeks 12 and 24

• Patient Global Impression Assessment

  Number of patients with improvement in PGIA. The Patient Global Impression Assessment questionnaire was completed at the end of Week 12 and end of Week 24. The scores were summarized by treatment group at each visit.

  From Baseline to Weeks 12 and 24

Secondary Outcomes (4)

• Spleen Length Reduction

  From Baseline to Weeks 24

• Frequency of RBC's or Platelet Transfusions

  At week 24

• Eastern Cooperative Oncology Group Performance Status

  At weeks 4, 12, 24, and 30 days post End-of-Treatment visit

• Number of Participants With Adverse Events

  Randomization through 30 days post End-of-Treatment visit

Study Arms (3)

Pacritinib 100 mg QD

EXPERIMENTAL

Drug: Pacritinib

Pacritinib 100 mg BID

EXPERIMENTAL

Drug: Pacritinib

Pacritinib 200 mg BID

EXPERIMENTAL

Drug: Pacritinib

Interventions

Pacritinib DRUG

Pacritinib

Pacritinib 100 mg BID; Pacritinib 100 mg QD; Pacritinib 200 mg BID

Eligibility Criteria

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

You may qualify if:

• PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)
• DIPSS Intermediate-1, Intermediate -2, or High-risk (Passamonti et al 2010)
• Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following:
• 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
• 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
• Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination
• 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
• Age ≥18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Peripheral blast count of \<10% throughout the Screening period
• Absolute neutrophil count of \>500/μL
• 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
• Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN
• Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan

You may not qualify if:

• Life expectancy \<6 months
• Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete allo-SCT
• History of splenectomy or planning to undergo splenectomy
• Splenic irradiation within the last 6 months
• Previously treated with pacritinib
• 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
• Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ≤100 mg per day, within the last 2 weeks
• Treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 inducer within the last 2 weeks
• Treatment with medications that can prolong the QTc interval within the last 2 weeks
• Treatment with an experimental therapy within the last 28 days
• 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)
• New York Heart Association Class II, III, or IV congestive heart failure
• 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)
• Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
• Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or constipation

Sponsors & Collaborators

• CTI BioPharma: lead

Study Sites (62)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Medical Faculty Associates, Inc.

Washington D.C., District of Columbia, 20037, United States

Location

Florida Cancer Specialists & Research Institute

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists & Research Institute

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida, 33401, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Saint Agnes Hospital

Baltimore, Maryland, 21229, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

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

San Antonio, Texas, 78229, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

CHU Hopital Sud

Amiens, 80054, France

Location

Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez

Lille, 59037, France

Location

CHU de Nimes - Hopital Universitaire Caremeau

Nîmes, 30029, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Universitaire de Toulouse- Hôpital Purpan

Toulouse, 31059, France

Location

SE AOK I. sx. Belgyogyaszati Klinika

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, 7400, Hungary

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura Dei Tumori

Meldola, 47014, Italy

Location

ASST Monza - Ospedale San Gerardo

Monza, 20900, Italy

Location

Yeungnam University Medical Center

Daegu, 42415, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

Skane University Hospital Lund

Lund, 22185, Sweden

Location

Orebro University Hospital

Örebro, 70185, Sweden

Location

Beatson West of Scotland Cancer Center

Glasgow, G12 0YN, United Kingdom

Location

Barts Health NHS Trust - The Royal London Hospital

London, E1 2ES, United Kingdom

Location

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

London, SE1 9RT, United Kingdom

Location

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34551507 DERIVED

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

Results Point of Contact

• Title: John Volpone SVP, Strategic Operations
• Organization: CTI BioPharma, Inc.

jvolpone@ctibiopharma.com

+1 (206) 272-4652

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 12, 2021
• Study Start: July 31, 2017
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: June 1, 2022
• Results First Posted: June 1, 2022

Record last verified: 2022-05

Locations

KR (4); GB (6); ES (4); HU (3); SE (2); IT (3); US (33); FR (7)