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

Primary Myelofibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04884191
• Other study ID #: PAC203
• Status: Completed
• Phase: Phase 2
• Start date: July 31, 2017
• Est. completion date: September 4, 2019

Study information

• Verified date: May 2022
• Source: CTI BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: September 4, 2019
• Est. primary completion date: September 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Post-Polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Pacritinib
Pacritinib

Locations

Country	Name	City	State
France	CHU Hopital Sud	Amiens
France	Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez	Lille Cedex
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 Cedex
Hungary	SE AOK I. sx. Belgyogyaszati Klinika	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura Dei Tumori	Meldola
Italy	ASST Monza - Ospedale San Gerardo	Monza
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Sweden	Skane University Hospital Lund	Lund
Sweden	Orebro University Hospital	Örebro
United Kingdom	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 States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Duke University Hospital	Durham	North Carolina
United States	Florida Cancer Specialists & Research Institute	Fort Myers	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Florida Cancer Specialists & Research Institute	Saint Petersburg	Florida
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio School of Medicine	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Cancer Institute	Stanford	California
United States	Medical Faculty Associates, Inc.	Washington	District of Columbia
United States	Florida Cancer Specialists & Research Institute	West Palm Beach	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Countries where clinical trial is conducted

United States,  France,  Hungary,  Italy,  Korea, Republic of,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percent Change in Spleen Volume	Percent change from baseline	From Baseline to Weeks 12 and 24
Primary	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
Primary	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	Spleen Length Reduction	Rate of reduction in spleen length from baseline	From Baseline to Weeks 24
Secondary	Frequency of RBC's or Platelet Transfusions	Number of patients	At week 24
Secondary	Eastern Cooperative Oncology Group Performance Status	0 = Fully active, able to carry on all pre-disease performance without restriction; = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; = Dead	At weeks 4, 12, 24, and 30 days post End-of-Treatment visit
Secondary	Number of Participants With Adverse Events		Randomization through 30 days post End-of-Treatment visit