Pacritinib for Myelofibrosis

(PACIFICA Trial)

Recruiting at 147 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Swedish Orphan Biovitrum

Must not be taking: CYP 3A4 inhibitors, Anticoagulants

Disqualifiers: Life expectancy <6 months, Splenectomy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

399 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called pacritinib for individuals with myelofibrosis, a type of bone marrow disorder, who have very low platelet levels. Participants will either take pacritinib or receive an alternative treatment chosen by their doctor, which may include options like low-dose ruxolitinib or hydroxyurea. The trial aims to determine if pacritinib can better manage symptoms and improve blood counts compared to other treatments. It seeks individuals diagnosed with primary myelofibrosis or related conditions who have a persistent, enlarged spleen and a platelet count below 50,000. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires stopping certain medications before starting, such as MF-directed therapies, strong CYP 3A4 inhibitors or inducers, and medications that increase bleeding risk or prolong the QT interval. There are specific timeframes for stopping these medications, like 14 days before treatment for some drugs. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pacritinib has been studied for treating myelofibrosis, a type of bone marrow disorder. It shows promise, especially for patients with limited treatment options due to low platelet counts. Some studies raised concerns about side effects like bleeding and heart issues, prompting further safety reviews. However, other research suggests it can effectively alleviate symptoms and reduce spleen size.

Pacritinib is in the later stages of testing, indicating that earlier studies have already assessed its safety. This trial aims to further understand its safety and effectiveness. Prospective participants should consider both the benefits and potential risks before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pacritinib for myelofibrosis because it offers a novel approach compared to current treatments. Unlike standard therapies like ruxolitinib, which primarily target the JAK2 pathway, pacritinib uniquely inhibits both JAK2 and IRAK1, potentially providing a broader range of symptom relief. Moreover, pacritinib is administered orally, making it convenient for patients who prefer not to have injections or infusions. This dual-target mechanism and ease of administration could make pacritinib a game-changer for those with myelofibrosis.

What evidence suggests that pacritinib might be an effective treatment for myelofibrosis?

Studies have shown that pacritinib can effectively treat myelofibrosis, particularly in patients with low platelet counts. In this trial, some participants will receive pacritinib, which research indicates reduces spleen size and improves symptoms in people with myelofibrosis, a condition characterized by scar tissue in the bone marrow. Clinical data support its use as both a first and second-line treatment for this condition. Pacritinib targets specific proteins involved in the disease, potentially managing symptoms better than some other treatments. Overall, evidence suggests pacritinib is a promising option for managing myelofibrosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Simran Singh

Principal Investigator

Sobi, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis who have severe thrombocytopenia (platelet count <50,000/μL). Participants must be adults with certain risk levels of the disease and able to tolerate MRI or CT scans. They should not have been treated with pacritinib before or other MF therapies recently and must not have significant recent bleeding history or certain heart conditions.

Inclusion Criteria

Provision of signed informed consent

I experience significant pain, itching, or night sweats due to my condition.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I haven't had serious heart issues in the last 6 months.

My heart's electrical cycle is longer than normal or I have low potassium/have a history of long QT syndrome.

I have an active or uncontrolled bowel disorder like Crohn's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pacritinib 200 mg BID or Physician's Choice therapy for up to 24 weeks

24 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

Extension

Participants benefiting from therapy may continue treatment until disease progression or intolerable adverse events

What Are the Treatments Tested in This Trial?

Interventions

• Pacritinib

Trial Overview The study tests Pacritinib (200 mg twice daily) against Physician's Choice medications in patients with specific types of myelofibrosis and severe low platelet counts. It randomly assigns participants in a 2:1 ratio to either Pacritinib or Physician's Choice therapy, aiming to enroll about 399 patients.

How Is the Trial Designed?

Group I: Pacritinib 200 mg BID Experimental Treatment 1 Intervention

To receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food

Group II: Physician's Choice (P/C) therapy Active Control 1 Intervention

The Physician's Choice (P/C) therapy (limited to single drugs from the following list: corticosteroids, hydroxyurea, danazol, or low-dose ruxolitinib). The proposed P/C regimen for a patient must be selected prior to randomization.

Pacritinib is already approved in United States for the following indications:

Approved in United States as Vonjo for:

• Intermediate or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10^9/L

Who Is Running the Clinical Trial?

Swedish Orphan Biovitrum

Lead Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

CTI BioPharma

Lead Sponsor

Trials

64

Recruited

5,400+

Dr. Adam R. Craig

CTI BioPharma

Chief Executive Officer since 2017

Member of the Royal College of Physicians (UK)

Dr. Monica Ravindra Shah

CTI BioPharma

Chief Medical Officer

MD from Brown Medical School

Sobi, Inc.

Industry Sponsor

Trials

14

Recruited

1,000+

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Published Research Related to This Trial

The combination of paclitaxel and vinorelbine was effective as a first-line treatment for untreated patients with metastatic lung adenocarcinoma, with a response rate of 50% and a median survival of 10 months based on a study of 54 patients.

While myelotoxicity was a common side effect affecting 87% of patients, severe neutropenia (grade 4) occurred in only 14.8%, indicating that the treatment regimen was manageable and did not require dose reductions for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. Stathopoulos, GP., Veslemes, M., Georgatou, N., et al.[2018]

In a study of 37 patients with advanced non-small cell lung cancer, the combination of paclitaxel and cisplatin showed a response rate of 28.6% in first-line treatment and 18.7% in second-line treatment, indicating some efficacy in managing the disease.

The treatment was associated with acceptable toxicity levels, with grade 3-4 leukopenia occurring in about 27.1% of first-line and 23.6% of second-line patients, suggesting that while the therapy is tolerable, further research with larger patient groups is needed to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. Rhee, EJ., Jeong, HS., Lee, SS.[2015]

Pacritinib was found to be well tolerated in patients with myelofibrosis, with a maximum tolerated dose established at 500 mg once daily and a recommended phase 2 dose of 400 mg once daily, showing manageable side effects and a low incidence of severe myelosuppression.

In the phase 2 part of the study, 23.5% of patients achieved a significant reduction in spleen volume after 24 weeks, indicating clinical activity, while 38.9% reported improved quality of life, highlighting its potential as an effective treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. Verstovsek, S., Odenike, O., Singer, JW., et al.[2022]

Pacritinib (VONJO™) is an oral kinase inhibitor approved in February 2022 for treating adults with intermediate- or high-risk myelofibrosis who have low platelet counts (below 50 × 10^9/L).

The approval was based on the phase III PERSIST-2 trial, which showed that pacritinib effectively reduced spleen volume in patients, indicating its efficacy in managing symptoms of myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib: First Approval. Lamb, YN.[2022]

EPO-906 is an intravenous drug being developed by Novartis Pharma AG that works as a microtubular depolymerization inhibitor, which means it helps stabilize microtubules in cells.

This drug is being investigated for its potential use in treating cancer, highlighting its role in targeting the cellular structures that are crucial for cancer cell division and growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EPO-906 (Novartis). Galmarini, CM., Dumontet, C.[2012]

In a study of 26 patients with brain metastases from non-small-cell lung cancer, the combination of paclitaxel and cisplatin with either vinorelbine or gemcitabine resulted in an intracranial response rate of 38%, indicating that this treatment can be effective for brain metastases.

The treatment was associated with manageable toxicity, with significant side effects like grade 3-4 neutropenia occurring in 31% of patients, and a median overall survival of 21.4 weeks, suggesting that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Cortes, J., Rodriguez, J., Aramendia, JM., et al.[2022]

Pacritinib is a promising treatment for myelofibrosis (MF) that targets multiple pathways, including JAK2 and FLT3, and has shown effectiveness in reducing splenomegaly and symptoms associated with the disease.

Unlike ruxolitinib, pacritinib has a lower risk of causing myelosuppression, making it a safer option for patients who experience cytopenias, with manageable gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia. Diaz, AE., Mesa, RA.[2021]

Ruxolitinib has been a key treatment for myelofibrosis for over a decade, but the emergence of new JAK inhibitors like fedratinib and pacritinib necessitates a clear understanding of what constitutes 'failure' of ruxolitinib therapy.

A consensus among experts suggests that in cases of ruxolitinib failure, either continuing ruxolitinib with an additional agent or switching to a different JAK inhibitor may be beneficial, highlighting the need for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. Bose, P., Kuykendall, AT., Miller, C., et al.[2023]

Pacritinib has shown promising efficacy in treating myelofibrosis (MF), with 31% of patients experiencing a significant reduction in spleen volume and 42% showing improvement in spleen size through physical examination after 24 weeks.

The treatment demonstrated a favorable safety profile, particularly for patients with preexisting anemia and thrombocytopenia, although common side effects included diarrhea and nausea, leading to treatment discontinuation in 26% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Komrokji, RS., Seymour, JF., Roberts, AW., et al.[2022]

In a study of 74 patients with advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel and cisplatin showed a 51% overall response rate, with a median survival time of 13.7 months, indicating its effectiveness as a first-line chemotherapy treatment.

The treatment was well-tolerated, with primarily nonhematological toxicities such as neuropathy and myalgia, and no severe hematological side effects like grade 3 or 4 neutropenia, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Paclitaxel and Cisplatin Combination Chemotherapy in Advanced Non-small-cell Lung Cancer. Lee, JA., Lee, KS., Ahn, JS., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03165734

NCT03165734 | A Phase 3 Study of Pacritinib in Patients ... The study is a randomized, controlled phase 3 study comparing the efficacy of pacritinib with P/C therapy in patients with PMF, PPV-MF, or PET-MF.

2. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/epjevy

Epjevy | European Medicines Agency (EMA) Epjevy was expected to be used to treat enlarged spleen and other symptoms of myelofibrosis, a disorder in which scar tissue builds up in the ...

3. vonjohcp.com vonjohcp.com/efficacy

VONJO® Efficacy Data Explore VONJO® (pacritinib) efficacy as a first and second-line treatment for patients with Myelofibrosis. View clinical trial data & learn more.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5146859/

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 ... An analysis of clinical exposures from the HCl and citrate salts of pacritinib was performed comparing Day 1 PK data from 12 patients who ...

5. clinicaltrial.be clinicaltrial.be/en/details/71362?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Phase 3 Study of Pacritinib in Patients With Primary My... The study is a randomized, controlled phase 3 study comparing the efficacy of pacritinib with P/C therapy in patients with PMF, PPV-MF, or PET-MF (Dynamic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9244834/

Retrospective analysis of pacritinib in patients with ... These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01773187

NCT01773187 | Pacritinib Versus Best Available Therapy ... Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with primary ...

8. ashpublications.org ashpublications.org/ashclinicalnews/news/2699/Long-Term-Safety-and-Efficacy-Data-for-Pacritinib

Long-Term Safety and Efficacy Data for Pacritinib in ... Authors presented new data about the safety and efficacy of pacritinib for myelofibrosis (MF): one featuring 60-week follow-up data from the PERSIST-1 study.

9. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Pacritinib_VONJO_in_Myelofibrosis_Monograph_May_2023.pdf

Pacritinib (VONJO) in Myelofibrosis National Drug ... The FDA placed a full clinical hold on pacritinib because of bleeding, cardiovascular, and fatal events in interim results for PERSIST-1, resulting in ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6578

Efficacy of pacritinib in patients with myelofibrosis who ... PAC at full dose demonstrates efficacy for spleen, symptoms, and transfusion response in pts with MF and both thrombocytopenia and anemia.