Pacritinib for Myelodysplastic Syndrome

Overseen By Ajoy L Dias, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, Antiplatelets, CYP3A4 inhibitors

Disqualifiers: Bleeding disorders, Cardiac conditions, Infections, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 8 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, pacritinib, for individuals with certain blood disorders, specifically myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN), which can sometimes progress to leukemia. Pacritinib may provide a new treatment option, particularly for those who have not responded to current therapies. The trial seeks participants with a confirmed diagnosis of MDS or MDS/MPN. Participants will take pacritinib capsules twice daily and attend regular check-ups to monitor their health and assess the treatment's effectiveness. As a Phase 1/Phase 2 trial, it aims to understand how pacritinib works in people and measure its effectiveness in an initial group, offering participants a chance to explore a potentially groundbreaking treatment.

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

The trial protocol does not specify if you must stop all current medications, but you cannot take certain medications that interact with the study drug, pacritinib. You must stop using strong inhibitors and inducers of CYP3A4 two weeks before starting the study drug. It's important to discuss your current medications with the trial team to ensure they don't interfere with the study.

Is there any evidence suggesting that pacritinib is likely to be safe for humans?

Research has shown that pacritinib is generally well-tolerated by patients with blood disorders. One study found that common side effects include diarrhea, nausea, and low blood cell counts, such as anemia (fewer red blood cells than normal) and thrombocytopenia (low platelet count). These side effects occurred in more than 20% of patients tested. Another analysis indicated that taking pacritinib at a dose of 200 mg twice a day is as safe as, or even safer than, other treatments. This suggests pacritinib could be a safer option for some patients. Overall, while some side effects are present, they are manageable, and pacritinib is considered a viable treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pacritinib is unique because it targets and inhibits specific enzymes called Janus kinases (JAKs), which are involved in the abnormal growth of blood cells seen in myelodysplastic syndrome (MDS). Unlike the standard treatments for MDS, which often involve chemotherapy or immunosuppressive therapies, pacritinib offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about pacritinib because it could provide a new option for patients who are not responding well to existing treatments, offering hope for improved outcomes.

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

Research has shown that pacritinib might help treat blood disorders like myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN). This trial will explore the effects of pacritinib in different cohorts. Studies have found that pacritinib, a type of medication known as a kinase inhibitor, can improve platelet counts and reduce symptoms in conditions like myelofibrosis. In people with myelofibrosis, pacritinib stabilized or even improved blood cell counts. These results suggest that pacritinib could offer similar benefits for those with MDS or MDS/MPN. ^{1 6 7 8 9}

Who Is on the Research Team?

Ajoy L Dias, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for children (12-17 years) and adults (18+ years) with blood disorders called Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms. Participants must be able to undergo various medical tests, including a bone marrow biopsy, and commit to an up-to-8-year study period with regular clinic visits.

Inclusion Criteria

I am 18 or older with LR-MDS and cannot take standard treatments.

I am 12-17 years old and weigh at least 35 kg.

Participants must meet specific performance status criteria

Exclusion Criteria

I am unwilling to accept blood transfusions.

I have a heart condition.

I do not have any uncontrolled illnesses or significant diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pacritinib orally in 28-day cycles, with weekly visits during cycle 1, bi-weekly visits during cycle 2, and gradually increasing to every 3 months after cycle 13. Treatment continues for up to 8 years.

Up to 8 years

Weekly visits during cycle 1, bi-weekly during cycle 2, every 3 months after cycle 13

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow biopsies, heart tests, and quality of life questionnaires.

30 days after last intervention

Visits as needed for monitoring

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pacritinib

Trial Overview The trial is testing pacritinib, a capsule taken orally twice daily in 28-day cycles. It's aimed at treating MDS and MDS/MPN by inhibiting certain enzymes that may affect these conditions. Dosages will vary among participants who are monitored over time through clinic visits and repeated tests.

How Is the Trial Designed?

Group I: 2/Phase II - Adult Experimental Treatment 1 Intervention

Low-risk cohort (cohort 2): Initiated on pacritinib 100 mg BID. After three cycles, pacritinib dose escalated to 200 mg BID, the adult phase II recommended dose, if not in complete remission.High-risk cohort (cohort 3): Initiated on pacritnib 200 mg BID, the adult phase II recommended dose.

Group II: 1/Phase I - Pediatric Experimental Treatment 1 Intervention

Escalating doses of pacritinib (cohort 1)

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 155 patients with myelodysplastic syndromes (MDS), vatalanib showed a modest hematological improvement in 5% of patients, with a higher response rate of 15% among those who remained on the treatment for at least 3 months.

While vatalanib delayed progression to acute myeloid leukemia (AML) and improved survival in low-risk patients (median overall survival of 36 months), its clinical use is limited due to significant side effects, including fatigue and nausea, and potential serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance). Gupta, P., Mulkey, F., Hasserjian, RP., et al.[2021]

A study of 54,953 patients with myelodysplastic syndromes (MDS) revealed that overall survival rates did not improve over time, despite the introduction of new treatments, indicating a need for further investigation into their effectiveness.

Younger patients (under 40 years old) were the only subgroup to show improved survival outcomes, while older patients and those with specific characteristics, such as refractory anemia with excess blasts, had worse survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Myelodysplastic Syndromes Over Time in the United States: A National Cancer Data Base Study From 2004-2013. Al-Kali, A., Zblewski, D., Foran, JM., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02469415?term=AREA%5BInterventionSearch%5D(%22Vidaza%22)&rank=5&tab=results

Study Results | Pacritinib for Patients With Lower-Risk ... Individual Patients: Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological ...

2. 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06303193

NCT06303193 | Pacritinib, a Kinase Inhibitor of CSF1R ... MDS and MDS/MPN can also progress to acute myeloid leukemia. Treatments for these disorders are risky and not always effective. Better treatments are needed.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10316250/

Long-term treatment with pacritinib on a compassionate ... Outcomes are particularly poor in patients with prior JAK2 inhibitor therapy: median survival in MF after discontinuing ruxolitinib is 14 months overall and ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18585

Treatment outcomes in patients with myelofibrosis and ... Real-world treatment outcomes demonstrate stability or improvement in PLT values in pts with MF and PLT ≥50 x10 9 /Ltreated with PAC.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12337178/

a real-world study based on FDA Adverse Event Reporting ... Thus, pacritinib is a safer option for MF patients with severe thrombocytopenia. A phase III trials observed hematologic AEs including anemia ...

7. vonjohcp.com vonjohcp.com/

VONJO® (pacritinib) HCP: VONJO® for Myelofibrosis Treatment In PERSIST-2, the most common adverse reactions in ≥20% of patients (n=106) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. Learn more ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02564536

Pacritinib in Combination With Low Dose Decitabine ... Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7058

Risk-adjusted safety analysis of pacritinib (PAC) in patients ... Risk-adjusted analysis demonstrates that the safety profile of PAC 200 mg BID is comparable or superior to BAT, including RUX.