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

Prior treatment

• 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.
• 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).
• 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).
• 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.

Other illness

• Severe (Child-Pugh C) liver impairment.
• 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
• Known seropositivity for human immunodeficiency virus. Known active hepatitis B, or C virus infection.
• 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.
• Any active GI or metabolic condition that could interfere with absorption of oral medication.

Lab values

• 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.
• 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).

Other

• Life expectancy \<6 months.
• Women who are pregnant or lactating

• 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.
• Willing to undergo and able to tolerate frequent MRI during the study and BM biopsy
• Able to understand and willing to complete symptom assessments.