Pacritinib For Bone Marrow Fibrosis In Patients With Myelofibrosis Who Have Thrombocytopenia

Sponsor
Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas
Study ID
NCT07394153
Phase
PHASE2
Status
Recruiting
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Conditions

  • Myelofibrosis，MF

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pacritinib — DRUG
    All patients enrolled will receive pacritinib 200 mg twice a day (BID). The maximum daily dose will be 400 mg of pacritinib. Pacritinib dose may be reduced by one level to 100 mg BID (200 mg total daily dose), or by two levels to 100 mg once daily (QD) for management of AEs. The treatment will be continued until progressive disease, unacceptable toxic effects, the patient no longer derives benefit from treatment, patients consent withdrawal or death, whichever occurs first.

Study Details

We hypothesize that pacritinib leads to modification of the myelofibrosis (MF) disease phenotype, especially related to BM fibrosis and cytopenias; due potentially to its dual effect as an inhibitor of the JAK and NFκB pathways, through its targets JAK2 and IRAK1 respectively, leading to a decrease of inflammatory cytokines and/or effects on stem/progenitor populations restoring hematopoiesis New evidence suggests that blocking simultaneously the JAK/STAT and NF-κB pathways might have a beneficial effect on aspects that only inhibition of the JAK pathway cannot achieve: partial recovery of BM histology and PACRIMYEL is a multicenter, open-label, single arm, phase II, exploratory study including patients with MF and platelet count between 50 - 120 x 109/L. Clinic visits will occur on weeks 4, 8, 12, 24, 36 and 52 during the first year and every 12 weeks during the second year of the treatment, and pacritinib will be dispensed at every visit to the clinic. Bone fibrosis will be assessed by biopsy and MRI imaging \[mDixon Quant "(Philips), IDEAL IQ (General Electric) or qDixon (Siemens)\] on weeks 24 and 52 after the first dose of study treatment. Splenomegaly and SVR (Splenic Volume Reduction) will be assessed by physical exam and MRI imaging on weeks 24 and 52 after the first dose of study treatment if splenomegaly at diagnosis. Same MRI to evaluate BM imaging will be used to measure spleen volume. Additionally, spleen size will be assessed by physical exam during the routine clinic visits. All patients should complete all efficacy assessments through Week 52, including patients who stop study treatment or have protocol-defined progressive disease prior to Week 24 and 52, unless the patient withdraws consent or dies. For patients who discontinue treatment before disease assessments on week 24 and week 52 for other reasons different than protocol-based progression of the disease (i.e. toxicity), and with no recent disease / fibrosis assessment (last BM biopsy \> 12 weeks), disease and fibrosis assessments will be performed by the end of treatment visit. The trial includes the assessment of safety (AEs, comorbidities) throughout the study period at every visit. Patient-reported symptoms through MPN-SAF TSS 2.0 will be collected screening, baseline (C1D1), and on Week 12, Week 24, Week 36, Week 52 and in 12-weeks intervals during the second year. Blood samples for translational research will be collected at screening and at week 24 for determination of cytokines.

Key Dates

Start date
Apr 15, 2026
Status verified
Apr 2026
Primary completion
Dec 31, 2027
Completion
Jun 30, 2028

Study Design

Enrollment
30 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: PACRIMYEL
    Pacritinib administed 200 mg twice a day (BID)

Primary Outcome Measure

Decrease in reticulin fibrosis in bone marrow (BM) [ Time Frame: from baseline to week 52 after first dose of study treatment ]

Central Contacts

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