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Evaluating Safety ,Tolerability, Pharmacokinetic,Efficacy of WJ01024 or WJ01024 Combined With Ruxolitinib in Patients With Myelofibrosis

2026年9月1日 更新者:zhou、Henan Cancer Hospital

A Phase I Clinical Study Evaluating the Safety and Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of Oral Administration of WJ01024 as a Monotherapy and in Combination With Ruxolitinib in Patients With Myelofibrosis

This is a Phase I clinical study to evaluate the safety and tolerability, pharmacokinetic characteristics and preliminary efficacy of oral WJ01024 administered as monotherapy and in combination with ruxolitinib in patients with myelofibrosis(MF). The study will be conducted in two phases: Phase IA and Phase IB.

Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant). Phase IB is a dose-escalation and dose-expansion study of WJ01024 in combination with ruxolitinib in JAKi-naïve patients with intermediate- or high-risk MF.

研究概览

地位

招聘中

详细说明

Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant).Dose escalation is carried out by combining accelerated titration and the traditional 3+3 design. During the accelerated titration phase, if no dose-limiting toxicity (DLT) and no ≥2 episodes of grade ≥2 treatment-related adverse events (TRAEs) occur within the first cycle (DLT observation period), no further subjects are enrolled at that dose level, and the study proceeds to the traditional 3+3 phase starting with the 60 mg group. At present, it is expected that the dose will be increased in four groups . If the researchers elects to explore intermediate doses or higher doses during the trial, adjustments will be made based on the actual situation. It is planned to expand the dosage by two groups. The final expanded dosage will be determined based on emerging safety and efficacy data. Dose escalation is stratified by background therapy (with vs. without background medication). Phase IB involves dose escalation and dose expansion studies of WJ01024 combined with ruxolitinib. Phase IB is planned to be conducted in JAKi-naïve patients with intermediate- or high-risk MF. Initiation of Phase IB requires that the group in Phase IA has completed the DLT observation period. Two combination dose groups are planned. Intermediate or higher doses may be explored at the investigator's discretion.Two combination dose levels are planned for expansion ;final expansion dose(s) will be determined based on emerging safety and efficacy data.

研究类型

介入性

注册 (估计的)

20

阶段

  • 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。

学习联系方式

学习地点

    • Henan
      • Zhengzhou、Henan、中国、450000
        • 招聘中
        • Henan Cancer Hospital
        • 接触:
        • 首席研究员:
          • Zhou Hu, Ph.D.

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

  • 孩子
  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. The subjects voluntarily participated in this study after obtaining full informed consent and signed the informed consent form.
  2. Age ≥18 years old, gender not limited;
  3. Patients diagnosed with primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or patients diagnosed with post-essential thrombocythemia MF (PET-MF) or post-polycythemia vera MF (PPV-MF) according to International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria;
  4. Patients evaluated as intermediate-1, intermediate-2, or high-risk according to the International Prognostic System (DIPSS) scoring system;;
  5. Expected life expectancy is ≥ 24 weeks;
  6. Eastern Cooperative Oncology Group (ECOG) score of 0-2 ;
  7. No planned for stem cell transplantation in the near future.
  8. Splenomegaly: Palpation of the spleen margin reaches or exceeds at least 5cm below the costal margin (the distance from the costal margin to the farthest point of the spleen protrusion), or spleen volume ≥450cm ³ by CT or MRI.
  9. Adequate hematological and organ function within 7 days before the first administration of the study drug (no RBC transfusion, growth factors, colony-stimulating factors, platelet-generating factors ,or platelet transfusion within 14 days before the testing) :

    • Absolute neutrophil count (ANC) ≥1.5×109/L;
    • Platelet count ≥75×109/L(Phase IA); Platelet count ≥100×109/L(Phase IB); Hemoglobin ≥ 8.0g /dL; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0× upper limit of normal (ULN); Total bilirubin ≤1.5×ULN; Creatinine ≤1.5×ULN.
  10. For women of childbearing age, within 7 days before the first administration, if the serum pregnancy test is confirmed to be negative and they agree to use effective contraceptive measures during the study drug period and within 90 days after the last administration. For male subjects whose sexual partners are women of childbearing age, they must agree to take effective contraceptive measures during the use of the study drug and within 90 days after the last administration.

Exclusion Criteria:

  • Peripheral blood blasts >5% or Bone marrow blasts >10%.
  • Previous treatment with XPO1 inhibitors.
  • Unable to cooperate with or unable to perform MRI or CT scans as deemed necessary by sponsor and investigator
  • Treatment with strong CYP3A inhibitors or inducers within 14 days prior to initial administration"

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:不适用
  • 介入模型:单组作业
  • 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:WJ01024 tablet
5-20mg BID (dosage per investigator judgement)

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
DLT
大体时间:12 months
Incidence of DLT
12 months
AE
大体时间:4 years
incidence and severity of adverse events(AEs) and serious adverse events(SAEs),as well as abnormal changes in clinical significance laboratory tests and other examinations
4 years
MTD
大体时间:12 months
Evaluate the Maximum tolerated dose
12 months
RP2D
大体时间:12 months
Evaluate the recommended dose for phase II
12 months

次要结果测量

结果测量
措施说明
大体时间
Pharmacokinetic (PK) Parameter
大体时间:1.5 years
The blood concentration of WJ01024
1.5 years
SVR35
大体时间:4 years
Percentage of subjects with spleen volume reduction of ≥35% (SVR35)
4 years
Score in MPN-SAF-TSS
大体时间:4 years
Percentage reduction in Total Symptom Score(TSS) and proportion of subjects achieving ≥50% reduction (TSS50) assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
4 years
incidence and severity of adverse events and serious adverse events
大体时间:4 years
incidence and severity of adverse events nd serious adverse events,as well as abnormal changes in clinical significance laboratory tests and other examinations
4 years
ORR:CR + PR + clinical improvement
大体时间:4 years
Overall response rate (ORR, CR + PR + clinical improvement) as determined by the investigator according to IWG-MRT criteria
4 years
LFS
大体时间:4 years
Leukemia-free survival (LFS) as assessed by the investigator
4 years
PFS
大体时间:4 years
Progression free survival (PFS) as assessed by the investigator
4 years
OS
大体时间:4 years
OS
4 years
LDH
大体时间:4 years
Evaluation of changes in serum LDH levels
4 years

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。

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)

2023年11月21日

初级完成 (估计的)

2026年9月26日

研究完成 (估计的)

2027年11月21日

研究注册日期

首次提交

2026年8月25日

首先提交符合 QC 标准的

2026年9月1日

首次发布 (实际的)

2026年9月3日

研究记录更新

最后更新发布 (实际的)

2026年9月3日

上次提交的符合 QC 标准的更新

2026年9月1日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

其他研究编号

  • JS110-002-I(T)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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