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地西他滨和 Venetoclax 与靶向突变 IDH1 抑制剂 Olutasidenib 联用的 1b/2 期研究

2026年9月30日 更新者：M.D. Anderson Cancer Center

To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Primary Objectives

  • Phase 1b: To determine the safety and tolerability and recommended phase 2 dose (RP2D) of decitabine (either IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib.
  • Phase 2: To determine the composite remission rate (CR, CRh and CRi) of decitabine (IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib for newly diagnosed (Arm A) or relapsed/refractory (Arm B) participants with IDH1-mutated myeloid malignancy.

Secondary Objectives

  • To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS)
  • To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.
  • To determine the overall response rate (CR, CRh, CRi, MLFS, and PR)
  • To characterize the pharmacokinetic (PK) profiles of venetoclax and olutasidenib in plasma samples (Phase 1b only).

Exploratory Objectives

- To investigate global gene expression profiles, DNA methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.

研究类型

介入性

注册 (估计的)

78

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。

学习联系方式

学习地点

  • 美国
    • Florida
      • Miami、Florida、美国、33136
        • 招聘中
        • University of Miami
        • 首席研究员：
          • Justin Watts, MD
        • 接触：
    • Kansas
      • Westwood、Kansas、美国、66205
        • 招聘中
        • The University of Kansas Medical Center
        • 接触：
        • 首席研究员：
          • Yacoub Abdulraheem, MD
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • 招聘中
        • Dana-Farber Cancer Institute
        • 首席研究员：
          • Jacqueline Garcia, MD
        • 接触：
    • New York
      • Buffalo、New York、美国、14263
    • Texas
      • Houston、Texas、美国、77030
        • 招聘中
        • MD Anderson Cancer Center
        • 接触：
        • 首席研究员：
          • Courtney DiNardo, MD

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

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Age > 18 years

  2. Participants must have a documented IDH1 gene mutation

  3. Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR

  4. Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only)

  5. To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:

    1. Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
    2. Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%).
    3. Creatinine clearance ≥30 mL/min to <45 mL/min.
    4. Moderate hepatic impairment with total bilirubin >1.5 to .3.0 x upper limit of normal (ULN)
    5. ECOG performance status of 2 or 3
    6. Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy

  6. Eastern Cooperative Oncology Group (ECOG) Performance Status </=2 (unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5e above)

  7. Adequate renal function including creatinine < 1.5, unless related to the disease or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5c above.

  8. Adequate hepatic function (direct bilirubin < 2x upper limit of normal (ULN) unless increase is due to Gilbert fs disease or leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible, or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5d above)

  9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.

  10. Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.

  11. Willing and able to provide informed consent.

Exclusion Criteria:

  1. Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML).
  2. Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
  3. Participants with active, uncontrolled leukemia involvement of the CNS
  4. Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant including active cGVHD requiring topic therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to start of study treatment.
  5. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
  6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
  7. Participant has a white blood cell count > 25 x 10^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.)
  8. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.

A) Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).

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：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：Part 1

Participants enrolled in Part 1, the dose of venetoclax/decitabine you receive will depend on when you join this study. Up to 3 dose levels will be tested. Up to 6 participants will be enrolled at each dose level.

- All participants will receive the same dose level of olutasidenib.
药品：Venetoclax

Given by PO

其他名称：
  • ABT-199
  • GDC-0199
药品：Decitabine

Given by IV

其他名称：
  • 达科根
药品：Olutasidenib

Given by PO

药品：Decitabine/cedazuridine

Given by PO

其他名称：
  • 英科威
  • ASTX727
实验性的：Part 2

Participants enrolled in Part 2, you will receive venetoclax/decitabine at the recommended dose that was found in Part 1.

- All participants will receive the same dose level of olutasidenib.
药品：Venetoclax

Given by PO

其他名称：
  • ABT-199
  • GDC-0199
药品：Decitabine

Given by IV

其他名称：
  • 达科根
药品：Olutasidenib

Given by PO

药品：Decitabine/cedazuridine

Given by PO

其他名称：
  • 英科威
  • ASTX727

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
Safety and adverse events (AEs)
大体时间：Through study completion; an average of 1 year.

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Through study completion; an average of 1 year.

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

M.D. Anderson Cancer Center

合作者

Rigel Pharmaceuticals,Inc.

调查人员

  • 首席研究员：Courtney DiNardo, MD、M.D. Anderson Cancer Center

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。

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)

2024年8月29日

初级完成 (估计的)

2027年6月30日

研究完成 (估计的)

2029年6月30日

研究注册日期

首次提交

2024年5月31日

首先提交符合 QC 标准的

2024年5月31日

首次发布 (实际的)

2024年6月6日

研究记录更新

最后更新发布 (实际的)

2026年10月5日

上次提交的符合 QC 标准的更新

2026年9月30日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 2024-0180
  • NCI-2024-04807 (其他标识符：NCI-CTRP Clinical Registry)

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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