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

NCT07394153 | Recruiting Phase 2

• 2 other identifiers: GEMFIN-MF-PACRI 24012025-522509-39-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Myelofibrosis，MF

Keywords

Myelofibrosis; JAK2 inhibitor; FTL3 inhibitor; pacritinib; low platelet count; IRAK1 inhibitor; Philadelphia Chromosome-negative Chronic Myeloproliferative Neoplasms; Bone fibrosis

Outcome Measures

Primary Outcomes (1)

• Decrease in reticulin fibrosis in bone marrow (BM)

  Measured in BM biopsy. Percentage of patients who experience a decrease of ≥1 grade in reticulin fibrosis from baseline to week 52. Definition of BM fibrosis grade will follow the European consensus that ranges from 0 (scattered, less fibrotic) to 3 (difuse and dense reticulin, more fibrotic). Patients will be classified as improvement (fibrosis decrease ≥1 grade), no change, or worsening (fibrosis increase \> 1 grade).

  from baseline to week 52 after first dose of study treatment

Secondary Outcomes (9)

• Improvement in BM fat fraction (FF)

  from baseline to week 52 after first dose of study treatment

• red blood cell (RBC) transfusion independence

  from baseline to week 24 and week 52 after first dose of study treatment

• Improvement in hemoglobin level

  from baseline to week 24 and week 52 after first dose of study treatment

• Improvement in platelet counts

  from baseline to week 24 and week 52 after first dose of study treatment

• Myeloproliferative neoplasms (MPN) driver-gen Variant Allele Frequency (VAF)

  Baseline and at Week 24 and Week 52 after the first dose of study treatment

Study Arms (1)

PACRIMYEL

EXPERIMENTAL

Pacritinib administed 200 mg twice a day (BID)

Drug: Pacritinib

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.

PACRIMYEL

Eligibility Criteria

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

You may qualify if:

• Signed written and voluntary informed consent.
• Age ≥18 years
• Patients with a confirmed diagnosis of myelofibrosis, either primary myelofibrosis (PMF) or post polycythemia vera (PPV-MF) or post essential thrombocythemia (PET-MF).
• Patients with thrombocytopenia, delimited by platelets counts between 50 - 120 x 109/L.
• Patients who require JAK-2 inhibitor therapy in the opinion of the investigator and are eligible to start treatment with pacritinib either in the first line (JAK2 inhibitor-naive) or in second line setting (after no response or loss of response or intolerance to one prior JAK2 inhibitor ).
• Note: patients should have recovered to grade ≤ 1 from any toxicity from previous treatment.
• Have a Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 - 2.
• Have a dynamic international prognostic scoring system (DIPSS) Intermediate-1, Intermediate-2, or High risk.
• Peripheral blasts count \< 5% and absolute neutrophil count (ANC) of ≥500/μL.
• Adequate liver and renal function, defined by:
• liver transaminases, including alanine aminotransferase (ALT or GOT) and aspartate aminotransferase (AST or GOT) ≤ 3 x upper limit normal (ULN). AST/ALT ≤5 × ULN if transaminase elevation is related to MF.
• Total bilirubin and/or direct bilirubin ≤ 4 x ULN.
• Estimated glomerular filtration rate (eGFR) \> 30 mL/min.
• Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN.
• If fertile, willing to use effective birth control methods during the study and up to 30 days after the last dose of pacritinib.

You may not qualify if:

• Life expectancy \<6 months.
• Splenic irradiation within the last 6 months.
• Previously treated with pacritinib.
• Concurrent enrollment in another interventional trial.
• Treatment with an experimental therapy within 28 days prior to the first dose of study treatment.
• Systemic treatment with a strong CYP3A4 inhibitor or inducer and the treatment cannot be either discontinued or switched to a different medication within 5 half-lifes prior to study entry.
• Severe (Child-Pugh C) liver impairment.
• Significant recent bleeding history defined as NCI CTCAE grade ≥2 within 3 months prior to first dose of study treatment, or with active bleeding, unless precipitated by an inciting event (e.g., surgery, trauma, or injury).
• QT corrected by the Fridericia method (QTcF) prolongation \>480 ms or other factors that increase the risk for QTcF interval prolongation (e.g., heart failure, hypokalemia or history of long QT interval syndrome).
• New York Heart Association Class II, III, or IV congestive heart failure.
• Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's disease, inflammatory bowel disease, chronic diarrhea or constipation
• Other malignancy within 3 years prior to treatment Day 1, other than curatively treated basal cell or squamous cell skin or corneal cancer; curatively treated carcinoma in situ of the cervix. The exception is if patients have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Known seropositivity for human immunodeficiency virus. Known active hepatitis B, or C virus infection.
• Women who are pregnant or lactating
• Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements.

Sponsors & Collaborators

• Swedish Orphan Biovitrum: collaborator
• MFAR Clinical Research S.L.: collaborator
• Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas: lead

Study Sites (13)

Hospital del Mar Barcelona

Barcelona, Barcelona, 08003, Spain

NOT YET RECRUITING

Hospital Universitario Vall d´Hebron

Barcelona, Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Universitario de Jerez

Jerez de la Frontera, Cádiz, 11407, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Fundación Jimenez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, Murcia, 30008, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

NOT YET RECRUITING

Hospital Clínico Universitario Valencia

Valencia, Valencia, 46010, Spain

NOT YET RECRUITING

Hospital General Universitario de Valencia

Valencia, Valencia, 46014, Spain

NOT YET RECRUITING

Hospital Universitario Doctor Peset

Valencia, Valencia, 46017, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

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)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Francisca Ferrer Marín, M.D.; Ph.D.

  Fundación Jimenez Díaz

  STUDY CHAIR

Central Study Contacts

A Responsible Person Designated by the sponsor, M.D., PhD.

CONTACT

0034934344412; investigacio@mfar.net

GEMFIN Secretary

CONTACT

0034934344412; secretaria@gemfin.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 6, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (13)