Pacritinib for Myelofibrosis|Thrombocytopenia

Inclusion criteria

• {"criterion_text":"- Signed written and voluntary informed consent.\n- Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN.\n- If fertile, willing to use effective birth control methods during the study and up to 30 days after the last dose of pacritinib\n- Willing to undergo and able to tolerate frequent MRI during the study and BM biopsy\n- Able to understand and willing to complete symptom assessments.\n- Age ≥18 years\n- Patients with a confirmed diagnosis of myelofibrosis, either primary myelofibrosis (PMF) or post polycythemia vera (PPV-MF) or post essential thrombocythemia (PET-MF)\n- Patients with thrombocytopenia, delimited by platelets counts between 50 - 120 x10e9/L.\n- 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.\n- Have a Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 - 2\n- Have a dynamic international prognostic scoring system (DIPSS) Intermediate-1, Intermediate-2, or High risk\n- Peripheral blasts count < 5% and absolute neutrophil count (ANC) of ≥500/μL.\n- Adequate liver and renal function, defined by: a. 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. b. Total bilirubin and/or direct bilirubin ≤ 4 x ULN. c. Estimated glomerular filtration rate (eGFR) > 30 mL/min."}

Exclusion criteria

• {"criterion_text":"- Life expectancy <6 months.\n- Any active GI or metabolic condition that could interfere with absorption of oral medication.\n- Splenic irradiation within the last 6 months.\n- Previously treated with pacritinib.\n- Concurrent enrollment in another interventional trial.\n- Treatment with an experimental therapy within 28 days prior to the first dose of study treatment.\n- 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.\n- Severe (Child-Pugh C) liver impairment.\n- 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).\n- 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).\n- Patients with rheumatoid arthritis for whom therapy with an alternative JAK inhibitor is required\n- 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.\n- 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).\n- New York Heart Association Class II, III, or IV congestive heart failure.\n- Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn’s disease, inflammatory bowel disease, chronic diarrhea or constipation\n- 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.\n- Known seropositivity for human immunodeficiency virus. Known active hepatitis B, or C virus infection.\n- Women who are pregnant or lactating\n- 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."}

Primary endpoints

• {"endpoint_text":"- Decrease of ≥1 grade in reticulin fibrosis from baseline to week 52 measured in bone marrow biopsy.","definition_or_measurement_approach":"Measured by bone marrow biopsy; a decrease of at least 1 grade in reticulin fibrosis from baseline to week 52."}

Secondary endpoints

• {"endpoint_text":"- Improvement in bone marrow fat fraction (FF) at Week 52 (C12D1) from baseline, measured by quantitative MRI as has been previously described","definition_or_measurement_approach":"Measured by quantitative MRI (Dixon Quant) comparing FF at Week 52 vs baseline."}
• {"endpoint_text":"- Percent change in fat fraction by quantitative Dixon Quant MRI will be correlated with improvement in BM fibrosis by at least 1 grade (assessment by BM biopsy) at Week 52.","definition_or_measurement_approach":"Correlation analysis between percent change in MRI fat fraction and ≥1 grade improvement in BM fibrosis by biopsy at Week 52."}
• {"endpoint_text":"- To evaluate anemia response a) Achievement of RBC transfusion independence over the first 24 weeks of treatment. b) Improvement in hemoglobin level without transfusion over the first 24 weeks of treatment c) Correlation study between i) the changes in hemoglobin level without transfusion and/or proportion of patients achievement of RBC transfusion independence with ii) the changes in the Bone Marrow (by MRI and/or BM biopsy) over the first 24 weeks of treatment.","definition_or_measurement_approach":"a) Proportion achieving RBC transfusion independence during first 24 weeks; b) change in Hb without transfusion over first 24 weeks; c) correlation analyses with MRI/BM biopsy changes."}
• {"endpoint_text":"- Durability of anemia response a) Achievement of RBC transfusion independence over the first 52 weeks of treatment. b) Improvement in hemoglobin level without transfusion over the first 52 weeks of treatment c) Correlation study between i) the changes in hemoglobin level without transfusion and/or proportion of patients achievement of RBC transfusion independence with ii) the changes in in the Bone Marrow (by MRI and/or BM biopsy) over the first 52 weeks","definition_or_measurement_approach":"a/b) As above over 52 weeks; c) correlation analyses with MRI/BM biopsy changes over 52 weeks."}
• {"endpoint_text":"- Improvement in platelet counts without transfusion at week 24 from baseline","definition_or_measurement_approach":"Change in platelet counts without transfusion at Week 24 vs baseline."}
• {"endpoint_text":"- Improvement in platelet counts without transfusion at week 52 from baseline","definition_or_measurement_approach":"Change in platelet counts without transfusion at Week 52 vs baseline."}
• {"endpoint_text":"- Post-treatment changes in MPN driver-gen VAF (JAK2, CALR, MPL) from baseline at Week 24 and Week 52.","definition_or_measurement_approach":"Measurement of variant allele frequency (VAF) for driver mutations (JAK2, CALR, MPL) at Weeks 24 and 52 compared to baseline."}
• {"endpoint_text":"- Percent change in fat fraction by quantitative Dixon Quant MRI and/or in the grade of fibrosis in BM will be correlated with the percent change in splenic volume; with the percent change in the driver-gen VAF; and with the hemoglobin and platelet levels at Week 24 and Week 52.","definition_or_measurement_approach":"Correlation analyses between MRI fat fraction/biopsy fibrosis grade and changes in spleen volume, driver-gen VAF, Hb and platelets at Weeks 24 and 52."}
• {"endpoint_text":"- Post-treatment changes in MPN driver-gen VAF will be correlated with the percent change in splenic volume; and with the hemoglobin and platelet levels at Week 24 and Week 52","definition_or_measurement_approach":"Correlation analyses between driver-gen VAF changes and spleen volume, Hb and platelet changes at Weeks 24 and 52."}
• {"endpoint_text":"- Frequency and severity of adverse events and Treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0","definition_or_measurement_approach":"Assessment and grading of AEs and TRAEs using NCI CTCAE v5.0."}
• {"endpoint_text":"- Rate of completion of pacritinib treatment: Cumulative dose Actual dose intensity Relative dose intensity Proportion of patients requiring dose interruptions Proportion of patients requiring dose reductions","definition_or_measurement_approach":"Descriptive measures: cumulative dose, actual and relative dose intensity, rates of dose interruptions and reductions."}
• {"endpoint_text":"- Assessement of MF or dual IRAK-1/JAK2 inhibitor (pacritinib) biology-related features associated with response: ● Changes in the levels of circulating plasma cytokines at week 24 from baseline by Luminex ● Changes in the mRNA and/or protein expression levels of of TGT betha and NFkB targets will be measures at week 24 in bone marrow and compare between responders and non-responders to pacritinib.","definition_or_measurement_approach":"Biomarker assessments: plasma cytokines by Luminex at Week 24 and mRNA/protein expression of TGF-beta and NFkB targets in BM at Week 24 compared between responders and non-responders."}
• {"endpoint_text":"- Decrease of ≥1 grade in reticulin fibrosis from baseline to week 24 measured in bone marrow biopsy.","definition_or_measurement_approach":"Measured by bone marrow biopsy; decrease ≥1 grade from baseline to Week 24."}
• {"endpoint_text":"- Improvement in bone marrow fat fraction (FF) at Week 24 from baseline, measured by quantitative MRI","definition_or_measurement_approach":"Measured by quantitative MRI comparing FF at Week 24 vs baseline."}
• {"endpoint_text":"- Percent change in fat fraction by quantitative Dixon Quant MRI and improvement in BM histology (assessment by BM biopsy) at Week 24.","definition_or_measurement_approach":"Correlation of percent change in MRI fat fraction with BM histology improvement by biopsy at Week 24."}
• {"endpoint_text":"- Changes in MPN symptoms throughout the study period assessed through MPN SAF TSS 2.0 questionnaire","definition_or_measurement_approach":"MPN SAF TSS 2.0 questionnaire scores across study visits."}
• {"endpoint_text":"- Percent change in splenic volume at Week 24 and Week 52 among patients with baseline splenomegaly","definition_or_measurement_approach":"Percent change in splenic volume measured by MRI at Weeks 24 and 52 in patients with baseline splenomegaly."}

Spain

Earliest CTIS Part Ii Submission Date

15-12-2025

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

53

Number Of Sites

13

Number Of Participants

30

Primary sponsor

Full Name

Grupo Espanol De Enfermedades Mieloproliferativas Cronicas Ph

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain