Pacritinib for bone marrow fibrosis in myelofibrosis with low platelets

Pacritinib For The Reduction Of Bone Marrow Fibrosis In Patients With Myelofibrosis Who Have Thrombocytopenia; A Multicenter, Open-Label, Single Arm, Phase II Exploratory Study

This trial will test if pacritinib can reduce bone marrow fibrosis and help restore blood counts in adults with myelofibrosis who have low platelets (50–120 × 10^9/L).

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas (other)
• Drugs / interventions: pacritinib
• Locations: 13 sites (Barcelona, Barcelona and 12 other locations)
• Trial ID: NCT07394153 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, single-arm Phase 2 trial enrolling adults with primary or post–PV/ET myelofibrosis and platelet counts between 50 and 120 × 10^9/L. Participants receive pacritinib with clinic visits at weeks 4, 8, 12, 24, 36 and 52 in year one and every 12 weeks in year two, and study drug is dispensed at each visit. Bone marrow fibrosis and hematologic parameters will be followed over time, alongside safety monitoring and assessments of clinical status. The study includes patients who are JAK2 inhibitor–naive or who have had prior JAK2 inhibitor treatment but meet stability and recovery criteria.

Who should consider this trial

Good fit: Adults (≥18 years) with confirmed primary or post–PV/ET myelofibrosis, platelet count 50–120 × 10^9/L, DIPSS intermediate‑1 to high risk, ECOG 0–2, and who are judged by the investigator to need JAK2 inhibitor therapy (either JAK2 inhibitor–naive or after one prior JAK2 inhibitor).

Not a fit: Patients with platelets below 50 × 10^9/L, very high blast counts, uncontrolled medical problems, or other contraindications to pacritinib are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, pacritinib could improve bone marrow structure and blood counts, which may reduce symptoms and transfusion needs for patients with thrombocytopenic myelofibrosis.

How similar studies have performed: Pacritinib has shown activity in prior myelofibrosis studies, particularly in patients with low platelets, but improvement of bone marrow fibrosis is a more exploratory outcome with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

1. Signed written and voluntary informed consent.
2. Age ≥18 years
3. Patients with a confirmed diagnosis of myelofibrosis, either primary myelofibrosis (PMF) or post polycythemia vera (PPV-MF) or post essential thrombocythemia (PET-MF).
4. Patients with thrombocytopenia, delimited by platelets counts between 50 - 120 x 109/L.
5. 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.
6. Have a Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 - 2.
7. Have a dynamic international prognostic scoring system (DIPSS) Intermediate-1, Intermediate-2, or High risk.
8. Peripheral blasts count \< 5% and absolute neutrophil count (ANC) of ≥500/μL.
9. Adequate liver and renal function, defined by:

   1. 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.
   2. Total bilirubin and/or direct bilirubin ≤ 4 x ULN.
   3. Estimated glomerular filtration rate (eGFR) \> 30 mL/min.
10. Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN.
11. If fertile, willing to use effective birth control methods during the study and up to 30 days after the last dose of pacritinib.
12. Willing to undergo and able to tolerate frequent MRI during the study and BM biopsy
13. Able to understand and willing to complete symptom assessments.

Exclusion Criteria:

1. Life expectancy \<6 months.
2. Splenic irradiation within the last 6 months.
3. Previously treated with pacritinib.
4. Concurrent enrollment in another interventional trial.
5. Treatment with an experimental therapy within 28 days prior to the first dose of study treatment.
6. 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.
7. Severe (Child-Pugh C) liver impairment.
8. 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).
9. Conditions or medications that increase the risk of bleeding, except for aspirin (dosages of ≤100 mg per day). Patients treated with "direct-acting oral anticoagulants (DOACs), could be considered for inclusion (may be consulted with the Sponsor, GEMFIN).
10. Any history of CTCAE grade ≥2 dysrhythmias or non-dysrhythmia cardiac conditions within 6 months prior to the first dose of study treatment. Patients with non-dysrhythmia or non-QTc grade 2 cardiovascular conditions , may be considered for inclusion, if stable , asymptomatic and unlikely to affect patient safety.
11. 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).
12. New York Heart Association Class II, III, or IV congestive heart failure.
13. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's disease, inflammatory bowel disease, chronic diarrhea or constipation
14. 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.
15. Known seropositivity for human immunodeficiency virus. Known active hepatitis B, or C virus infection.
16. Women who are pregnant or lactating
17. 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.
18. Any active GI or metabolic condition that could interfere with absorption of oral medication.

Where this trial is running

Barcelona, Barcelona and 12 other locations

• Hospital del Mar Barcelona — Barcelona, Barcelona, Spain (NOT_YET_RECRUITING)
• Hospital Universitario Vall d´Hebron — Barcelona, Barcelona, Spain (NOT_YET_RECRUITING)
• Hospital Clinic de Barcelona — Barcelona, Barcelona, Spain (RECRUITING)
• Hospital Universitario de Jerez — Jerez de la Frontera, Cádiz, Spain (NOT_YET_RECRUITING)
• Hospital General Universitario Gregorio Marañon — Madrid, Madrid, Spain (RECRUITING)
• Hospital Universitario Ramon y Cajal — Madrid, Madrid, Spain (RECRUITING)
• Fundación Jimenez Díaz — Madrid, Madrid, Spain (RECRUITING)
• Hospital Universitario 12 de Octubre — Madrid, Madrid, Spain (RECRUITING)
• Hospital General Universitario Morales Meseguer — Murcia, Murcia, Spain (RECRUITING)
• Hospital Universitario de Salamanca — Salamanca, Salamanca, Spain (NOT_YET_RECRUITING)
• Hospital Clínico Universitario Valencia — Valencia, Valencia, Spain (NOT_YET_RECRUITING)
• Hospital General Universitario de Valencia — Valencia, Valencia, Spain (NOT_YET_RECRUITING)
• Hospital Universitario Doctor Peset — Valencia, Valencia, Spain (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: A Responsible Person Designated by the sponsor, M.D., PhD.

Conditions: Myelofibrosis，MF, Myelofibrosis, JAK2 inhibitor, FTL3 inhibitor, pacritinib, low platelet count, IRAK1 inhibitor, Philadelphia Chromosome-negative Chronic Myeloproliferative Neoplasms