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INCB000928 作为单一疗法或与 Ruxolitinib 联合治疗因骨髓增生性疾病导致贫血的参与者 (LIMBER)

2026年5月12日 更新者：Incyte Corporation

INCB000928 作为单一疗法或与 Ruxolitinib 联合治疗因骨髓增生性疾病导致贫血的参与者的 1/2 期开放标签多中心研究

这项 1/2 期、开放标签、剂量探索研究旨在评估 INCB000928 作为单一疗法或与 ruxolitinib 联合用于输血依赖或出现的 MF 参与者的安全性和耐受性、PK、PD 和疗效有症状的贫血。 这项研究将包括两部分：剂量递增和扩展。

研究概览

地位

主动，不招人

条件

干预/治疗

研究类型

介入性

注册 (实际的)

84

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 加拿大
    • Ontario
      • Toronto、Ontario、加拿大、M5G 2M9
        • Princess Margaret Cancer Center
    • Quebec
      • Montreal、Quebec、加拿大、H3T1E2
        • McGill University Jewish General Hospital
  • 意大利
      • Bergamo、意大利、24127
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Bologna、意大利、40138
        • S Orsolas University Hospital Seragnoli Institute of Hematology
      • Florence、意大利、50134
        • Azienda Ospedaliero-Universitaria Careggi (Aouc)
      • Orbassano、意大利、10043
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
      • Pavia、意大利、27100
        • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
      • Perugia、意大利、06124
        • Ospedale Santa Maria Della Misericordia Perugia
  • 日本
      • Bunkyō City、日本、113-8519
        • Tokyo Medical and Dental University Hospital
      • Chiba、日本、260-8717
        • Chiba Cancer Center
      • Gifu、日本、500-8513
        • Gifu Municipal Hospital
      • Hirakata、日本、573-1191
        • Kansai Medical University Hospital
      • Kumamoto、日本、862-8655
        • Kumamoto Shinto General Hospital
      • Osaka、日本、541-8567
        • Osaka International Cancer Institute
  • 法国
      • Angers、法国、49033
        • Centre Hospitalier D'Angers
      • Marseille、法国、13273
        • Institut Paoli Calmettes
      • Paris、法国、75010
        • Hospital Saint Louis
  • 美国
    • California
      • Duarte、California、美国、91010
        • City of Hope National Medical Center
      • Irvine、California、美国、92618
        • City of Hope Orange County
      • Los Angeles、California、美国、90089
        • USC Norris Comprehensive Cancer Center
      • Palo Alto、California、美国、94304
        • Stanford Cancer Center
      • San Diego、California、美国、92103
        • Prebys Cancer Center
    • Georgia
      • Atlanta、Georgia、美国、30322
        • Emory University - Winship Cancer Institute
      • Atlanta、Georgia、美国、30322
        • Emory University-Winship Cancer Institute
    • Michigan
      • Grand Rapids、Michigan、美国、49546
        • START MidWest
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University School of Medicine
    • New York
      • New York、New York、美国、10065
        • Weill Cornell Medical Centers
    • North Carolina
      • Durham、North Carolina、美国、27705
        • Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
    • Tennessee
      • Nashville、Tennessee、美国、37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston、Texas、美国、77030
        • MD Anderson Cancer Center
  • 英国
      • Boston、英国、PE21 9QS
        • United Lincolnshire Hospitals
      • Lincoln、英国、LN2 5QY
        • Lincoln County Hospital
      • Truro、英国、TR1 3LJ
        • Royal Cornwall Hospital Truro Sunrise Centre
    • WLS
      • Cardiff、WLS、英国、CF14 4XW
        • University Hospital of Wales

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  • 依赖输血或出现症状性贫血的 MF 参与者，定义如下：

    1. 贫血：在筛查期间记录的 Hgb 值 < 10 g/dL，两次测量之间至少间隔 7 天（注意：红细胞输注必须在筛查期间 Hgb 测量前至少 2 周）。
    2. 依赖输血：参与者在第 1 周期第 1 天之前的 28 天内接受了至少 4 个单位的红细胞输注，或者在第 1 个周期第 1 天之前的 8 周内平均接受了至少 4 个单位的红细胞输注，持续在没有出血或治疗引起的贫血的情况下，Hgb 水平 < 8.5 g/dL。 此外，最近一次输血事件必须发生在第 1 周期第 1 天之前的 28 天内。

  • 以下 ECOG 体能状态评分：

    1. 剂量递增阶段为 0 或 1。
    2. 剂量扩展阶段为 0、1 或 2。
  • 预期寿命大于6个月
  • 避免怀孕或生育孩子的协议。
  • 没有资格接受或没有对可用的贫血疗法（如 ESAs）做出反应。
  • 对于 TGA：
  • 先前接受 JAK 抑制剂治疗至少 12 周的参与者。
  • 根据 IWG-MRT 标准，具有中级 2 或高 DIPSS MF 的参与者。
  • 对于 TGB：
  • 参与者必须在首次研究治疗之前至少连续 12 周接受稳定的鲁索替尼治疗方案。
  • 根据 IWG-MRT 标准，具有中级 1、中级 2 或高 DIPSS MF 的参与者。

排除标准：

  • 接受过任何先前的同种异体或自体干细胞移植或此类移植的候选人。
  • 任何先前的化学疗法、免疫调节药物疗法、免疫抑制疗法、生物疗法、内分泌疗法、靶向疗法、抗体或低甲基化剂来治疗参与者的疾病，但仅用于 TGB 的 ruxolitinib 除外，在 5 个半衰期或 28 天内（以时间为准）更短）在研究治疗的第一剂之前。
  • 筛选时超出协议定义范围的实验室值。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：治疗组 B (TGB)
INCB000928 将与 ruxolitinib 联合使用。
药品：INCB000928
INCB000928将以方案规定的剂量给药。
药品：鲁索替尼
鲁索替尼将以方案规定的剂量给药。
实验性的：治疗组 A (TGA)
INCB000928 将每天给药一次（QD）。
药品：INCB000928
INCB000928将以方案规定的剂量给药。
实验性的：治疗组 C (TGC)
INCB000928 将与鲁索替尼联合给药。
药品：INCB000928
INCB000928将以方案规定的剂量给药。
药品：鲁索替尼
鲁索替尼将以方案规定的剂量给药。

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
大体时间：up to approximately 4 years
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug/treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug.
up to approximately 4 years
Number of Participants With Any ≥Grade 3 TEAE and Any Treatment-emergent SAE
大体时间：up to approximately 4 years
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. 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.
up to approximately 4 years
Number of Participants With Dose-limiting Toxicities (DLTs)
大体时间：from Cycle 1 Day 1 to Cycle 1 Day 28
A DLT was defined as the occurrence of any protocol-defined toxicity occurring during the first treatment cycle, from Cycle 1 Day 1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT-Evaluable Population included all non-backfill participants eligible for dose escalation who met the criteria outlined in the Analysis Population field.
from Cycle 1 Day 1 to Cycle 1 Day 28
Maximum Tolerated Dose (MTD)
大体时间：from Cycle 1 Day 1 to Cycle 1 Day 28
The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. Per the protocol, the stopping rule was either (a) reaching a certain number of participants at one dose level under the early stopping rule or (b) reaching the pre-defined maximum sample size. Dose escalation was to be considered complete only when one of these conditions was met. After completion, the MTD was to be defined as the dose level closest to the target DLT rate. The MTD could not be concluded until the stopping rule was met.
from Cycle 1 Day 1 to Cycle 1 Day 28
Recommended Dose for Expansion (RDE)
大体时间：from Cycle 1 Day 1 to Cycle 1 Day 28
The RDE was defined as a pharmacodynamically active dose. The RDE was determined in an independent fashion by evaluation of all available data (i.e., safety, pharmacokinetic, and pharmacodynamic data) from the respective dose-escalation stage of the study for further investigation in the expansion cohort, including safety (e.g., low-grade but chronic toxicities, dose reduction, dose interruption, or missed doses of zilurgisertib and/or ruxolitinib). The RDE(s) could not exceed the MTD in each treatment group
from Cycle 1 Day 1 to Cycle 1 Day 28

次要结果测量

结果测量
措施说明
大体时间
从周期 1 第 15 天到周期 7 第 1 天铁调素的百分比变化
大体时间：从周期 1 第 15 天到周期 7 第 1 天
百分比变化计算为（[基线后值减去基线值]/[基线值]）* 100。
从周期 1 第 15 天到周期 7 第 1 天
Percentage of Participants With Anemia Response
大体时间：up to Week 24
Anemia response was defined as (a) a hemoglobin (Hgb) increase of 1.5 grams per deciliter (g/dL) relative to baseline for any "rolling" 12-week period (84 days with each assessment that met this requirement) during the first 24 weeks of treatment if transfusion independent (TI) at baseline; or (b) transfusion independence for any "rolling" 12-week period (absence of any red blood cell [RBC] transfusion over any 84-day period) during the first 24 weeks of treatment if transfusion dependent (TD) at baseline.
up to Week 24
Duration of Anemia Response
大体时间：up to 1530 days
Duration of anemia response was defined as (a) the interval from the first onset of anemia response to the earliest date of loss of anemia response that persisted for at least 4 weeks or death from any cause (for TI participants at baseline); or (b) the duration of the RBC-TI period for participants who achieved RBC-TI for at least 12 consecutive weeks during the first 24 weeks of treatment (for TD participants at baseline).
up to 1530 days
Mean Change From Baseline in the Hgb Value Over 12-week Treatment Periods
大体时间：Baseline; up to 24 weeks
Mean change from baseline was assessed as the largest increase from baseline in the mean Hgb values over any rolling 12-week treatment period during the first 24 weeks of treatment. Change from baseline was calculated as the post-baseline value minus the baseline value.
Baseline; up to 24 weeks
Rate of Red Blood Cell (RBC) Transfusion From Week 24 Through Week 48
大体时间：from Week 24 through Week 48
The rate of RBC transfusion was defined as the average number of RBC units per participant-month during the treatment period.
from Week 24 through Week 48
Splenic Volume Response Rate at Week 24
大体时间：Week 24
Splenic volume response rate was defined as the percentage of participants achieving a ≥35% reduction in spleen volume at Week 24 relative to baseline as measured by magnetic resonance imaging or computed tomography scan.
Week 24
Spleen Length Response
大体时间：Week 24
Spleen length response was defined as the percentage of participants achieving a ≥50% reduction in spleen length at any visit relative to baseline as measured by palpation.
Week 24
Overall Response Rate (ORR)
大体时间：Week 24
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) (including the morphologic effects of the combination of zilurgisertib with ruxolitinib on bone marrow) according to Tefferi et al (2013) definitions.
Week 24
Progression-free Survival (PFS)
大体时间：Week 24
PFS was defined as the interval from the first dose of study treatment until the first documented progression or death according to Tefferi et al (2013) definitions.
Week 24
Leukemia-free Survival (LFS)
大体时间：Week 24
LFS was defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause.
Week 24
Cmax of Zilurgisertib Alone
大体时间：Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Cmax was defined as the maximum concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Tmax of Zilurgisertib
大体时间：Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
tmax was defined as the time to the maximum concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
AUC0-t of Zilurgisertib
大体时间：Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
AUC0-t was defined as the area under the plasma concentration-time curve from time 0 to the last quantifiable measurable plasma concentration of zilurgisertib.
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
Change From Baseline in Ferritin
大体时间：Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
Change from Baseline (CFB) was calculated as the post-Baseline value minus the Baseline value.
Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
Change From Baseline in Hemoglobin at the End of Treatment
大体时间：up to 1530 days
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
up to 1530 days

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Incyte Corporation

调查人员

  • 研究主任：Amanda McBride, MD、Incyte Corporation

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2021年3月19日

初级完成 (实际的)

2025年4月1日

研究完成 (估计的)

2027年11月26日

研究注册日期

首次提交

2020年6月19日

首先提交符合 QC 标准的

2020年6月29日

首次发布 (实际的)

2020年7月2日

研究记录更新

最后更新发布 (实际的)

2026年5月14日

上次提交的符合 QC 标准的更新

2026年5月12日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • INCB 00928-104
  • 2020-004029-21 (EudraCT编号)
  • 2023-503625-19-00 (注册表标识符：EU CT Number)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

在提交研究计划后，Incyte 与合格的外部研究人员共享数据。 这些请求由审查小组根据科学价值审查和批准。 提供的所有数据均已匿名，以根据适用法律法规尊重参与试验患者的隐私。

试验数据可用性根据 https://www.incyte.com/our-company/compliance-and-transparency 中描述的标准和流程

IPD 共享时间框架

数据将在首次发表后或市场授权产品和适应症的研究结束 2 年后共享。

IPD 共享访问标准

合格研究的数据将根据 www.incyteclinicaltrials.com 的数据共享部分中描述的标准和流程与合格的研究人员共享 网站。 对于批准的请求，研究人员将根据数据共享协议的条款被授予访问匿名数据的权限。

IPD 共享支持信息类型

  • 研究方案
  • 树液

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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