Pacritinib for Myelofibrosis

(PACIFICA Trial)

Recruiting at 112 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

Trial Summary

What is the purpose of this trial?

This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count \<50,000/μL). Approximately 399 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 266 patients) or to P/C therapy (approximately 133 patients) Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis Intervention/treatment: Drug-Pacritinib

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.

What data supports the effectiveness of the drug Pacritinib for treating myelofibrosis?

Pacritinib has shown effectiveness in reducing spleen size and symptoms in patients with myelofibrosis, especially those with low platelet counts, as demonstrated in the phase III PERSIST-2 trial. It is a selective inhibitor targeting specific proteins involved in the disease, and it has been approved for use in the USA based on these results. ^{1 2 3 4 5}

What makes the drug Pacritinib unique for treating myelofibrosis?

Pacritinib is unique because it specifically targets and inhibits certain proteins (called JAK2 and FLT3) involved in the abnormal blood cell production seen in myelofibrosis, offering a different approach compared to other treatments that may not target these proteins. ^{6 7 8 9 10}

Research Team

Simran Singh

Principal Investigator

Sobi, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pacritinib: First Approval. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. [2018]

7. England pubmed.ncbi.nlm.nih.gov

EPO-906 (Novartis). [2012]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. [2015]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

A Phase II Study of Paclitaxel and Cisplatin Combination Chemotherapy in Advanced Non-small-cell Lung Cancer. [2015]