Phase I/II Trial of Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
National Cancer Institute (NCI)
Summary
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.
Description
Background: -Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral cytopenia, ineffective and dysplastic hematopoiesis, and increased risk of progression to acute myeloid leukemia (AML). -The significant genetic heterogeneity of MDS contributes to the challenges in treatment. * Targeting the bone marrow microenvironment (BMME) may allow for treatments that bypass the genetic complexity of MDS. * MDS studies support a role for changes within the BMME and support the emerging concept that interdependency between the MDS clone a…
Eligibility
- Age range
- 12–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Participants must have histologically or cytologically confirmed MDS or MDS/MPN, including therapy-related MDS or MDS/MPN, and MDS or MDS/MPN with germline predisposition, by the Department of Laboratory Medicine Hematology Laboratory, CC or by the Laboratory of Pathology, NCI as defined according to the 2016 WHO criteria, 2022 WHO criteria, or 2022 International Consensus Classification * Age 12-17 years for phase I and age \>= 18 years for phase II * Participants \>= 18 years of age with HR-MDS must have resistance to hypomethylating agents as defined as failure to sh…
Interventions
- Drugpacritinib
Pacritinib will be administered orally on a continuous basis for 28 day cycles without a rest period between cycles. Dose assigned by dose level/phase.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland