2025-522509-39-00招募中2 期
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
Grupo Español de Enfermedades Mieloproliferativas Crónicas Filadelfia Negativas13 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2026年2月6日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Decrease of ≥1 grade in reticulin fibrosis from baseline to week 52 measured in bone marrow biopsy.
研究概览
简要总结
The primary objective of this study is to evaluate the effect of pacritinib on the bone marrow fibrosis.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Signed written and voluntary informed consent.
- •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.
- •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 x10e9/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: 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.
排除标准
- •Life expectancy <6 months.
- •Any active GI or metabolic condition that could interfere with absorption of oral medication.
- •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).
- •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).
- •Patients with rheumatoid arthritis for whom therapy with an alternative JAK inhibitor is required
- •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).
- •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.
结局指标
主要结局
Decrease of ≥1 grade in reticulin fibrosis from baseline to week 52 measured in bone marrow biopsy.
Decrease of ≥1 grade in reticulin fibrosis from baseline to week 52 measured in bone marrow biopsy.
次要结局
- 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.
- 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
- Frequency and severity of adverse events and Treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0
- 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
- Improvement in bone marrow fat fraction (FF) at Week 52 (C12D1) from baseline, measured by quantitative MRI as has been previously described
- 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.
- 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.
- Decrease of ≥1 grade in reticulin fibrosis from baseline to week 24 measured in bone marrow biopsy.
- Improvement in bone marrow fat fraction (FF) at Week 24 from baseline, measured by quantitative MRI
- Percent change in fat fraction by quantitative Dixon Quant MRI and improvement in BM histology (assessment by BM biopsy) at Week 24.
- 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.
- 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
- Improvement in platelet counts without transfusion at week 24 from baseline
- Changes in MPN symptoms throughout the study period assessed through MPN SAF TSS 2.0 questionnaire
- Percent change in splenic volume at Week 24 and Week 52 among patients with baseline splenomegaly
- Improvement in platelet counts without transfusion at week 52 from baseline
- Post-treatment changes in MPN driver-gen VAF (JAK2, CALR, MPL) from baseline at Week 24 and Week 52.
研究者
GEMFIN Secretariat
Scientific
Grupo Español de Enfermedades Mieloproliferativas Crónicas Filadelfia Negativas
研究点 (13)
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