A study comparing current standard therapies with pacritinib taken by mouth for the treatment of myelofibrosis (either diagnosed alone or after polycythemia vera or essential thrombocytopenia) in patients with a low platelet count

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2013-004000-19-GB
• Date of registration: 21/02/2014
• Prospective Registration: Yes
• Primary sponsor: CTI BioPharma Corp.
• Public title: A study comparing current standard therapies with pacritinib taken by mouth for the treatment of myelofibrosis (either diagnosed alone or after polycythemia vera or essential thrombocytopenia) in patients with a low platelet count
• Scientific title: A Randomized Controlled Phase 3 Study of Oral Pacritinib versus Best Available Therapy in Patients with Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis - PERSIST-2
• Date of first enrolment: 30/05/2014
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004000-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: yes; Other: yes; Other trial design description: Open study as Investigator and patients unblinded, but central data review and Sponsor are blinded.; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: best available therapy; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Netherlands, New Zealand, Russian Federation, United Kingdom, United States

Contacts

• Name: Regulatory Director
• Affiliation: CTI Life Sciences Ltd.

• Name: Regulatory Director
• Affiliation: CTI Life Sciences Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Intermediate-1 or -2 or high-risk PMF, PPV-MF, or PET-MF
2. Thrombocytopenia (platelet count =100,000/µL) at any time after signing informed consent
3. Informed consent may be signed up to 35 days prior to randomization
4. Palpable splenomegaly =5 cm below the LCM in midclavicular line by physical examination
5. Total Symptom Score (TSS) =13 on the MPN-SAF-TSS 2.0, not including the inactivity question
6. Age =18 years old
7. ECOG performance status 0 to 3
8. Peripheral blast count <10%
9. Absolute neutrophil count (ANC) >500/µL
10. Patients who are platelet or RBC transfusion-dependent are eligible
11. Adequate liver and renal function, defined by liver transaminases (AST/SGOT and ALT/SGPT) =3 × ULN (AST/ALT =5 × ULN if transaminase elevation is related to MF), direct bilirubin =4 x ULN, and creatinine =2.5 mg/dL
12. At least 6 months from prior splenic irradiation
13. At least 12 months from prior 32P therapy
14. At least 1 week since prior treatment (most recent dose) with a potent cytochrome P450 3A4 (CYP3A4) inhibitor
15. At least 2 weeks since receiving any treatment for PMF, PPV-MF, or PET-MF
16. If fertile, males and females must agree to use effective birth control methods during the study.
17. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study
18. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument
19. Able to understand and willing to sign the informed consent form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion criteria:
1. Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication
2. Life expectancy less than 6 months
3. Prior treatment with more than 2 JAK2 inhibitors or pacritinib
4. There is no maximum cumulative prior JAK2 inhibitor treatment (approved or investigational)
5. Completed allogeneic stem cell transplantation (ASCT) or are eligible for and willing to complete ASCT
6. History of splenectomy or planning to undergo splenectomy
7. Uncontrolled intercurrent illness, including but not limited to ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements
8. Active bleeding requiring hospitalization during the screening period
9. 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
10. Inflammatory or chronic functional bowel disorder, such as Crohn’s disease, inflammatory bowel disease, chronic diarrhea, or constipation
11. Clinically symptomatic and uncontrolled cardiovascular disease
12. History of any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure
13. New York Heart Association Class III or IV congestive heart failure
14. Patients with National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) 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 patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade =3, corrected QT interval (QTc) prolongation >450 ms, or other factors that increase the risk for QT 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).
15. Erythropoietic agent within 28 days prior to randomization
16. Thrombopoietic agent within 14 days prior to randomization
17. Known seropositivity for human immunodeficiency virus (HIV)
18. Known active hepatitis A, B, or C virus infection
19. Women who are pregnant or lactating


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis with Thrombocytopenia
MedDRA version: 18.1 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: pacritinib
Product Code: SB1518
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: pacritinib
CAS Number: 937272-79-2
Current Sponsor code: pacritinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. MRI or CT assessments at: Screening and Wk 24 (additional exploratory evaluation at weeks 12, 36, 48 and every 12 weeks).
2. TSS: assessed daily through week 48 of the study or until the patient discontinues study treatment, whichever occurs first.

Main Objective: The primary objective is to compare the efficacy of two dose-schedule arm(s) of pacritinib (pooled once daily [QD] and twice-daily [BID] dosing arms) with that of best available therapy (BAT) in patients with thrombocytopenia and primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF).

Secondary Objective: The secondary objectives are:
1. To compare the efficacy of QD pacritinib with that of BAT, as assessed by the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24 by MRI or CT and the proportion of patients achieving a = 50% reduction in the TSS from baseline to Week 24 on the MPN-SAF TSS 2.0.
2. To compare the efficacy of BID pacritinib with that of BAT, as assessed by the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24 by MRI or CT and the proportion of patients achieving a = 50% reduction in the TSS from baseline to Week 24 on the MPN-SAF TSS 2.0.

Primary end point(s): 1. the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan;
2. the proportion of patients achieving a = 50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not Applicable

Secondary end point(s): Not Applicable

Secondary ID(s)

2013-004000-19-BE

PAC326

Source(s) of Monetary Support

CTI BioPharma Corp.

Ethics review

Status: Approved
Approval date: 30/05/2014
Contact:

Results

• Results available: Yes
• Date Posted: 11/08/2018
• Date Completed: 26/04/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004000-19/results