160 Participants Needed

Pacritinib for Myelodysplastic Syndrome

RN
AM
Overseen ByAlain Mina, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

Background: Myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are blood disorders that can cause serious complications in children and adults. 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. Objective: To test a study drug (pacritinib) in adults and children with MDS or MDS/MPN. Eligibility: Children (aged 12 to 17 years) and adults (aged 18 years and older) with MDS or MDS/MPN. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart function. They may have a bone marrow biopsy: An area over the hip will be numbed; a needle will be inserted to remove a sample of soft tissue from inside the hipbone. Pacritinib is a capsule taken by mouth. All participants will take the study drug 2 times a day, every day, in 28-day cycles. They will write down the date and time they take each capsule. Doctors will assign varying dosages of the drug to different participants. Participants will have clinic visits each week during cycle 1; every 2 weeks during cycle 2; and gradually increasing to every 3 months after cycle 13. Treatment will continue for up to 8 years. Bone marrow biopsies, heart tests, and other tests will be repeated at intervals throughout the study. Participants will also fill out questionnaires about their quality of life, the symptoms of their disease, and other topics.

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.

How is the drug Pacritinib unique for treating myelodysplastic syndrome?

Pacritinib is unique because it is a targeted therapy that inhibits specific enzymes (kinases) involved in cell growth and survival, which may help manage myelodysplastic syndrome by addressing the underlying disease mechanisms. This approach differs from traditional treatments that may not specifically target these pathways.12345

Research Team

AM

Alain Mina, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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
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Exclusion Criteria

I am unwilling to accept blood transfusions.
I have a heart condition.
I do not have any uncontrolled illnesses or significant diseases.
See 7 more

Timeline

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

Treatment Details

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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: 2/Phase II - AdultExperimental Treatment1 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 - PediatricExperimental Treatment1 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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.
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.
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]

References

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). [2021]
Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712. [2023]
Outcome of Myelodysplastic Syndromes Over Time in the United States: A National Cancer Data Base Study From 2004-2013. [2020]
An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614). [2020]
Efficacy of growth factors compared to other therapies for low-risk myelodysplastic syndromes. [2007]