Study of INCB053914 in Subjects With Advanced Malignancies
2021年11月9日 更新者：Incyte Corporation
A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies.
The study will be conducted in 4 parts.
Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study).
Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s).
Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).
研究概览
地位
终止
条件
研究类型
介入性
注册 (实际的)
97
阶段
- 阶段2
- 阶段1
扩展访问
得到正式认可的 出售给公众。
查看扩展访问记录。
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
-
-
Arizona
-
Tucson、Arizona、美国、85719
- The University of Arizona Cancer Center
-
-
California
-
Sacramento、California、美国、95817
- UC Davis Comprehensive Cancer Center
-
Santa Monica、California、美国、90095
- UCLA Medical Hematology & Oncology
-
-
Connecticut
-
New Haven、Connecticut、美国、06511
- Yale University
-
-
Florida
-
Jacksonville、Florida、美国、32224
- Mayo Clinic Florida
-
Sarasota、Florida、美国、33916
- Florida Cancer Specialists & Research Institute
-
Tampa、Florida、美国、33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Georgia
-
Atlanta、Georgia、美国、30322
- Emory University-Winship Cancer Institute
-
-
Maryland
-
Baltimore、Maryland、美国、21201
- University of Maryland
-
-
Massachusetts
-
Boston、Massachusetts、美国、02215
- Dana-Farber Cancer Center
-
-
Michigan
-
Ann Arbor、Michigan、美国、48109
- University Of Michigan Comprehensive Cancer Center
-
-
Nebraska
-
Omaha、Nebraska、美国、69198
- University of Nebraska Medical Center
-
-
Ohio
-
Cincinnati、Ohio、美国、45236
- Oncology Hematology Care Clinical Trials LLC
-
-
Oklahoma
-
Oklahoma City、Oklahoma、美国、73104
- Stephenson Cancer Center
-
-
Tennessee
-
Nashville、Tennessee、美国、37232
- Vanderbilt University Medical Center
-
Nashville、Tennessee、美国、37203
- Tennessee Oncology
-
-
Texas
-
Austin、Texas、美国、78705
- Texas Oncology
-
Tyler、Texas、美国、75702
- Texas Oncology
-
-
Wisconsin
-
Milwaukee、Wisconsin、美国、53226
- Medical College of Wisconsin
-
-
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:
- Aged 18 years or older
- Confirmed diagnosis of select advanced malignancy
Parts 1 and 2:
- Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
- Not currently a candidate for curative treatment
Parts 3 and 4:
- Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Eastern Cooperative Oncology Group (ECOG) performance status
- Part 1: 0 or 1
- Parts 2, 3 and 4: 0, 1, or 2
- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.
Exclusion Criteria:
- Inadequate bone marrow or organ function
- Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
- Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
- Prior receipt of a PIM inhibitor
- Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
- Screening corrected QT interval (QTc) interval > 470 milliseconds
- Radiotherapy within the 2 weeks prior to initiation of treatment
- Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment
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：Parts 1 and 2: INCB053914 100 mg QD
INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
实验性的：Parts 3 and 4: INCB053914 + Azacitidine
Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Azacitidine dose will be 75 mg/m^2.
Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
其他名称：
|
|
实验性的：Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Cytarabine dose will be 1 g/m^2.
Cytarabine will be administered as an intravenous (IV) infusion.
|
|
实验性的：Parts 3 and 4: INCB053914 + Ruxolitinib
Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
|
|
实验性的：Parts 1 and 2: INCB053914 50 mg
INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
实验性的：Parts 1 and 2: INB053914 65 mg
INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
实验性的：Parts 1 and 2: INB053914 80 mg
INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
实验性的：Parts 1 and 2: INB053914 100 mg BID
INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
实验性的：Parts 1 and 2: INB053914 115 mg
INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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 |
|---|---|---|
|
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
大体时间：Approximately 7 months
|
Approximately 7 months
|
|
|
Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
大体时间：Approximately 2 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
|
Approximately 2 months
|
|
Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
大体时间：Approximately 6 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
|
Approximately 6 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
大体时间：1 month
|
Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
|
1 month
|
|
Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
大体时间：Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
大体时间：Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
大体时间：Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
大体时间：Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
大体时间：Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
大体时间：Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
大体时间：Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
大体时间：Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
大体时间：Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
大体时间：Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Tmax of INCB053914 Monotherapy
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: CL/F of INCB053914 Monotherapy
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of INCB053914 Monotherapy
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Ctau of INCB053914 Monotherapy
大体时间：Cycle 1 Day 8
|
Cycle 1 Day 8
|
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)
2015年12月29日
初级完成 (实际的)
2020年8月11日
研究完成 (实际的)
2020年8月11日
研究注册日期
首次提交
2015年10月26日
首先提交符合 QC 标准的
2015年10月26日
首次发布 (估计)
2015年10月27日
研究记录更新
最后更新发布 (实际的)
2021年12月8日
上次提交的符合 QC 标准的更新
2021年11月9日
最后验证
2021年11月1日
更多信息
与本研究相关的术语
关键字
其他研究编号
- INCB 53914-101
药物和器械信息、研究文件
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.