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

NCT06303193 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001554001554-C
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic Syndrome; bone marrow disorder; Myelodysplasia; myeloproliferative disorders; pediatric bone marrow failure; 5q deletion; multi-lineage dysplasia; Clonal Hematopoiesis; Aplastic Anemia

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose of pacritinib in participants 12-17 years of age

  Determined by the number of participants with dose-limiting toxicities (DLTs) reported at each dose level studied

  28 days

• Efficacy as measured by Objective Response Rate (ORR) per each risk-based cohort

  Clinical responses evaluated by CBC and bone marrow biopsy/aspirate reported separately by cohort, with a separate 95% confidence interval for each cohort

  After every cycle (C4D1, C7D1, C10D1, C16D1) and yearly after

Secondary Outcomes (2)

• Pharmacokinetic (PK) properties of pacritinib

  28 days

• Extended safety of pacritinib

  Day 1 of study drug through 30 days after the last intervention

Study Arms (2)

1/Phase I - Pediatric

EXPERIMENTAL

Escalating doses of pacritinib (cohort 1)

Drug: pacritinib

2/Phase II - Adult

EXPERIMENTAL

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.

Drug: pacritinib

Interventions

pacritinib DRUG

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.

1/Phase I - Pediatric; 2/Phase II - Adult

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 show improvement after at least 4 cycles of treatment (primary resistance) or relapse in participants with initial response to long-term treatment (secondary resistance) OR have intolerance to hypomethylating agents OR have a contraindication to hypomethylating agents
• Participants \>= 18 years of age with LR-MDS must be refractory to or ineligible to receive standard of care therapies, i.e. erythropoietin-stimulating agents, lenalidomide, luspatercept, and present with one of the following characteristics:
• Severe neutropenia defined by absolute neutrophils count \<=0.5(SqrRoot) 10\^9/L without the use of granulocyte colony-stimulating factors
• Symptomatic anemia defined by hemoglobin 16-week average \<10 g/dL and symptoms that may include fatigue, weakness, reduced exercise tolerance, dyspnea on exertion, palpitations, (orthostatic) hypotension, near syncope and restless legs
• Thrombocytopenia defined as platelets \<20(SqrRoot) 10\^9/L or platelets \<50(SqrRoot) 10\^9/L and a history of clinically relevant non-major or major bleeding according to the ISTH classification
• Participants 12-17 years of age with MDS must be relapsed/refractory OR ineligible to receive immunosuppressive therapy and hematopoietic stem cell transplantation
• Ineligibility to receive hematopoietic stem cell transplantation will include participants who are not anticipated to be candidates to receive transplantation within the next 3 months due to medical comorbidities, lack of appropriate donor, or logistical barriers to transplant
• Participants with MDS/MPN must be relapsed/refractory (failed a minimum of 1 standard of care therapy) OR ineligible to receive standard of care OR without known life-prolonging therapy options OR have a diagnosis for which no known standard of care exists
• Participants 12-17 years of age must weigh \>= 35 kg
• If any of the prior therapies noted below were given to the participant, they must have been completed within the following timeframes:
• days from last dose of short-acting myeloid growth factors (i.e., filgrastim) and \>= 14 days for long-acting (i.e., pegfilgrastim)
• days from last dose of short-acting thrombopoietic growth factors (i.e.,eltrombopag) and \>= 28 days for long-acting (i.e., romiplostim)
• days or 5 pharmacokinetic half-lives from biological therapy agent

You may not qualify if:

• Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10 K/mcL with transfusions
• Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe (grade \>= 3) unprovoked bleeding complications in the one year prior to enrollment, or any unprovoked grade 2 bleeding complications in the 3 months prior
• to enrollment
• Use of anti-platelet or anticoagulant medication other than low-dose aspirin (100 mg daily or less) in the 14 days prior to enrollment, or any ongoing requirement for these medications
• Participants who are unwilling to accept blood transfusions
• Participants with ANC \< 500 cells/mcL AND hospitalization for a fungal infection in the 12 months prior to enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib
• Concomitant administration with sensitive substrates/narrow therapeutic index drugs of CYP3A4, CYP1A2, P-gp BCRP, and OCT1 should be avoided. Concurrent use of strong inhibitors and inducers of CYP3A4 are not allowed. Prior use is allowed as long as medication is stopped two weeks prior to study drug initiation. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Concomitant administration of medications with significant potential to cause QTc prolongation.
• Participants with the following cardiac conditions at screening:
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Uncontrolled cardiac dysrhythmias
• QTc(F) prolongation \>450 ms, or other factors that increase the risk for QT prolongation (i.e., heart failure, or a history of long QT interval syndrome)
• Grade \>= 3 cardiac complication in the 6 months prior to enrollment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Kouroukli O, Symeonidis A, Foukas P, Maragkou MK, Kourea EP. Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes. Cancers (Basel). 2022 Nov 17;14(22):5656. doi: 10.3390/cancers14225656.

  PMID: 36428749 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes; Bone Marrow Diseases; Anemia, Refractory, with Excess of Blasts; Myeloproliferative Disorders; Anemia, Aplastic

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Bone Marrow Failure Disorders

Study Officials

• Najla El Jurdi, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rania S Hishmeh, R.N.

CONTACT

(240) 858-3681; rania.hishmeh@nih.gov

Najla El Jurdi, M.D.

CONTACT

(240) 992-4033; najla.eljurdi@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 12, 2024
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2035
• Last Updated: May 6, 2026

Record last verified: 2026-03-25

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)