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Ruxolitinib in Combination With Nilotinib in Chronic Myeloid Leukemia (CML) Patients

A Phase I Study of Ruxolitinib in Combination With Nilotinib in CML Patients With Evidence of Molecular Disease

This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML).

研究概览

研究类型

介入性

注册 (实际的)

11

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。

学习地点

    • Florida
      • Tampa、Florida、美国、33612
        • H. Lee Moffitt Cancer Center and Research Institute

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:

  • Must have chronic phase chronic myeloid leukemia (CML). They must also be under treatment with nilotinib as either first, second, or third-line therapy.
  • Must have a complete cytogenetic response (CCyR) OR must have been on nilotinib for a minimum of 6 months.
  • Must not have undergone treatment for any other form of cancer (aside from non-melanoma skin cancer) in the past 5 years.
  • 18 years of age or older and must be able to speak and read English or Spanish.
  • Able to provide informed consent.
  • Prior therapy with a tyrosine kinase inhibitor (TKI) other than nilotinib is allowable, however, nilotinib must be the current therapy. All participants must be under the care of a Moffitt Cancer Center physician, and enrollment is expected to be complete within 6 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%.
  • Must have normal organ and marrow function as defined in study protocol.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Ruxolitinib and nilotinib administration. Women of child-bearing age will be required to have a negative pregnancy test within 14 days of enrolling in this study.
  • Ability to understand and the willingness to sign a written informed consent document
  • B-HCG will be performed on all women of child-bearing potential as screening prior to enrollment on this trial. STAT3 levels in the bone marrow will also be measured prior to enrollment.

Exclusion Criteria:

  • Patients who are in accelerated phase or blast phase CML.
  • May not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in the study.
  • Known history of a prolonged QT interval (QTc >480).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study. Women who are breast feeding their infants should discontinue this practice if the mother is treated with ruxolitinib.
  • Currently receiving any drugs considered to be strong CYP3A4 inducers or inhibitors which cannot be discontinued or changed to an alternative drug prior to enrolling on the trial.
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.
  • Patients receiving nilotinib 200 mg by mouth, twice a day (PO BID) or a lower dose are not eligible.

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:Nilotinib with Ruxolitinib

The starting dose of ruxolitinib will be 5mg by mouth (PO) twice a day (BID) and will increase by 5 mg increments in each cohort, to a maximum dose of 15 mg PO BID. Nilotinib will be given at a dose ranging from 300 mg PO BID to 400 mg PO BID, depending on the participant's dose prior to enrollment on the trial.

Dose Level 1: Ruxolitinib 5 mg twice a day (BID); Nilotinib 300 mg or 400 mg BID.

Dose Level 2: Ruxolitinib 10 mg BID; Nilotinib 300 mg or 400 mg BID.

Dose Level 3: Ruxolitinib 15 mg BID; Nilotinib 300 mg or 400 mg BID.

Participants will remain on the same dose of nilotinib they have been receiving prior to enrollment on the trial. This will range from 300 mg PO BID to 400 mg PO BID.

Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose of ruxolitinib, based on the number of dose.

其他名称:
  • 塔西尼亚
  • BCR-ABL kinase inhibitor
Dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose, based on the number of dose limiting toxicities seen at a specific dose.
其他名称:
  • INCB018424

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
Phase I: Maximum Tolerated Dose (MTD)
大体时间:Average of 6 months

Maximum tolerated dose (MTD) of ruxolitinib with nilotinib. Dose escalation will follow a 3+3 study design. If 2 or more participants within a cohort experience a dose limiting toxicity (DLT), then the MTD will have been exceeded and the preceding dose level will be evaluated as the MTD. A minimum of 6 participants must be evaluated at the dose level in order for it to be declared as the MTD.

Dose limiting toxicity is defined as:

  • Any non-hematological toxicity ≥ grade three, excluding any untreated nausea, vomiting, diarrhea or fatigue that occurs during the first 56 days of therapy.
  • Grade three thrombocytopenia with active bleeding or grade four thrombocytopenia or febrile neutropenia (ANC <500 cells/µL and fever > 101.0 F (38.5C)).
  • Any treatment related grade five toxicity (i.e., death).
Average of 6 months

其他结果措施

结果测量
措施说明
大体时间
Complete Molecular Response Rate
大体时间:Up to 36 months
Complete molecular response rate (CMR >4.5 log reduction) after the treatment combination.
Up to 36 months

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。

合作者

调查人员

  • 首席研究员:Kendra Sweet, M.D.、H. Lee Moffitt Cancer Center and Research Institute

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。

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)

2013年2月21日

初级完成 (实际的)

2016年10月17日

研究完成 (实际的)

2019年1月9日

研究注册日期

首次提交

2012年10月3日

首先提交符合 QC 标准的

2012年10月4日

首次发布 (估计)

2012年10月5日

研究记录更新

最后更新发布 (实际的)

2021年1月5日

上次提交的符合 QC 标准的更新

2021年1月4日

最后验证

2021年1月1日

更多信息

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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