A 2-Part, Phase 2, Open-Label Study of the Safety, Tolerability, and Efficacy of Itacitinib Immediate Release in Participants With Primary Myelofibrosis or Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis) Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 21
- 主要终点
- Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
This is a 2-part study. In Part 1, participants will be dosed at 2 different dose levels in order to select the RP2D for Part 2 of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of primary MF meeting the 2016 WHO criteria for overt PMF or secondary MF (PPV-MF or PET-MF) meeting the 2008 IWG-MRT criteria.
- •At least Intermediate 1 risk MF according to the DIPSS.
- •Prior treatment with ruxolitinib and/or fedratinib monotherapy
- •Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF.
- •Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume ≥ 450 cm3 on imaging assessed during screening.
- •Allogeneic stem cell transplant not planned.
- •Platelet is greater than or equal to 50 × 109/L at screening.
- •Ability to comprehend and willingness to sign a written ICF for the study.
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib
- •Record of ≥ 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening
- •For participants on ruxolitinib or fedratinib, unable to be tapered from that treatment over the course of 14 days without corticosteroids, hydroxyurea, or other agents
- •Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1
- •Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib
- •Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement
- •Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study
- •ECOG performance status ≥ 3
- •Life expectancy less than 24 weeks
- •Not willing to receive RBC or platelet transfusions
- •Participants with laboratory values at screening outside of protocol defined ranges
- •Significant concurrent, uncontrolled medical condition
- •Participants with impaired cardiac function or clinically significant cardiac disease unless approved by medical monitor/sponsor
- •History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful
- •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
- •Evidence of HBV or HCV infection or risk of reactivation
- •Known HIV infection.
研究组 & 干预措施
Part 1 : Dose Escalation of itacitinib
Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level.
干预措施: itacitinib (Drug)
Part 2 : Dose Expansion of itacitinib
Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1.
干预措施: itacitinib (Drug)
结局指标
主要结局
Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to 724 days
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
Part 1: Number of Participants With Any Grade 3 or Higher TEAE
时间窗: up to 724 days
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
Part 2: Splenic Response Rate (SRR) at Week 24
时间窗: Baseline; Week 24
SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline.
次要结局
- Part 2: Number of Participants With Any TEAE(up to at least 24 weeks)
- Part 2: Number of Participants With Any Grade 3 or Higher TEAE(up to at least 24 weeks)
- Part 2: Total Symptom Score (TSS) Response Rate at Week 24(Baseline; Week 24)
- Part 2: Mean Change (From Day 1 Versus Week 12 and Week 24) in the 5 Multi-item Functional Scale Scores and the Multi-item Global Health Status Scale Score (EORTC QLQ-C30)(Baseline; Weeks 12 and 24)
- Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC)(Baseline; Week 24)