Authorised Therapeutic confirmatory (Phase III) Post-Essential Thrombocythaemia Myelofibrosis

PACIFICA: A Phase 3 Study of Pacritinib in Patients with Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

EU CTIS ID: 2024-515953-52-00

What this study is testing

1. To compare the efficacy of pacritinib with that of physician’s choice (P/C) therapy, as assessed by the proportion of participants achieving a ≥35% spleen volume reduction (SVR) from baseline at Week 24 as measured by magnetic resonance imaging (MRI; preferred) or computed tomography (CT) scans 2. To compare the efficacy of pacritinib with P/C therapy, as assessed by the proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) from baseline at Week 24

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF
10. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition scan
11. 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), total bilirubin ≤4 × ULN (in cases where total bilirubin is elevated, direct bilirubin ≤4 × ULN is required), and creatinine ≤2.5 mg/dL
12. Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
13. If fertile, willing to use highly effective birth control methods during the trial
14. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study

You likely can't join if

1. Life expectancy <6 months
10. Treatment with an experimental therapy, including MF-directed experimental therapies within 28 days prior to treatment Day 1
11. Systemic treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or a strong CYP3A4 inducer within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1
12. Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (eg, surgery, trauma, or injury)
13. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), and daily use of cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1. Treatment with systemic anti-vascular endothelial growth factor (anti-VEGF) agents within 28 days prior to treatment Day 1.
14. Systemic treatment with medications that can prolong the QT interval within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1

See the full eligibility criteria

Who can join

1. Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF
10. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition scan
11. 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), total bilirubin ≤4 × ULN (in cases where total bilirubin is elevated, direct bilirubin ≤4 × ULN is required), and creatinine ≤2.5 mg/dL
12. Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
13. If fertile, willing to use highly effective birth control methods during the trial
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 patient-reported outcome instrument
16. Provision of signed informed consent
2. Platelet count of <50,000/μL at Screening (Day -35 to Day -3)
3. Dynamic International Prognostic Scoring System Intermediate-1, Intermediate-2, or High-Risk
4. Palpable splenomegaly ≥5 cm below the lower costal margin in the midclavicular line as assessed by physical examination
5. TSS of ≥10 on the MPN-SAF TSS 2.0 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats. The TSS criteria need only to be met on a single day
6. Age ≥18 years
7. Eastern Cooperative Oncology Group performance status 0 to 2
8. Peripheral blast count of <10% throughout the Screening period prior to randomization
9. Absolute neutrophil count of ≥500/μL

What rules you out

1. Life expectancy <6 months
10. Treatment with an experimental therapy, including MF-directed experimental therapies within 28 days prior to treatment Day 1
11. Systemic treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or a strong CYP3A4 inducer within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1
12. Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (eg, surgery, trauma, or injury)
13. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), and daily use of cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1. Treatment with systemic anti-vascular endothelial growth factor (anti-VEGF) agents within 28 days prior to treatment Day 1.
14. Systemic treatment with medications that can prolong the QT interval within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1
15. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within 6 months prior to treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, after consultation with the Medical Monitor, if stable and unlikely to affect patient safety
16. Any history of CTCAE grade ≥2 cardiac dysrhythmias within 6 months prior to treatment Day 1. Patients with non-corrected QT interval CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, after consultation with the Medical Monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety
17. QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors that increase the risk for QT interval prolongation (eg, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or history of long QT interval syndrome)
18. New York Heart Association Class II, III, or IV congestive heart failure
19. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
2. Completed allogeneic stem cell transplant, or are eligible for and willing to complete other approved available therapy including allogeneic stem cell transplant
20. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn’s Disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation
21. Other malignancy within 3 years prior to treatment Day 1. The following patients may be eligible despite having had a malignancy within the prior 3 years: patients with curatively treated squamous or basal cell carcinoma of the skin; patients with curatively treated non-invasive cancers; patients with organ-confined prostate cancer with prostate specific antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low, Low, or Favorable Intermediate; and patients with curatively treated non-metastatic prostate cancer with negative PSA
22. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the Investigator, would limit compliance with trial requirements
23. Known seropositivity for human immunodeficiency (HIV) virus. For patients in Czech Republic, France, and Italy only: testing for HIV is required during Screening
24. Known active hepatitis A, B, or C virus infection. For patients in Czech Republic, France, and Italy only: testing for hepatitis B and C is required during Screening
25. Women who are pregnant or lactating
26. Concurrent enrollment in another interventional trial
27. Severe thrombocytopenia due to vitamin B12 deficiency, folate deficiency, or viral infection in the opinion of the investigator
28. Known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate; any contraindication to the “physician’s choice” medicinal product selected by the investigator to be used as the comparator or to loperamide or equivalent antidiarrheal medication
29. Persons deprived of their liberty by a judicial or administrative decision
3. History of splenectomy or planning to undergo splenectomy
30. Persons subject to legal protection measures or unable to express their consent
31. Temporarily incapacitated persons
4. Splenic irradiation within the last 6 months
5. Previously treated with pacritinib
6. Treatment with any MF-directed therapy within 14 days prior to treatment Day 1
7. Prior treatment with more than one JAK2 inhibitor
8. Prior treatment with ruxolitinib, if BOTH of the following conditions are met: i. exposure to higher-dose ruxolitinib (>10 mg daily) within 120 days prior to treatment Day 1; AND ii. total duration of treatment with higher-dose ruxolitinib (>10 mg daily) was >90 days, from first to last exposure (i.e., this 90-day period starts on the date of first administration of ruxolitinib at a total daily dose of >10 mg and continues for 90 calendar days, regardless of whether higher-dose ruxolitinib is administered continuously or intermittently
9. Prior treatment with any JAK2 inhibitor other than ruxolitinib, irrespective of dose, with a duration of >90 days. The 90-day period starts on the date of first administration of JAK2 inhibitor therapy and continues for 90 calendar days, regardless of whether therapy is administered continuously or intermittently

The study team makes the final eligibility decision.

Where it's taking place

Israel
Bosnia and Herzegovina
Russian Federation
Australia
United States
Kazakhstan
Belarus
Ukraine
United Kingdom
Japan
Serbia
India
Canada
Korea, Republic of
Georgia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Israel; Bosnia and Herzegovina; Russian Federation; Australia; United States; Kazakhstan and 9 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.