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Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

2014年12月22日 更新者:National Cancer Institute (NCI)

Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia

This phase I trial studies the side effects and best dose of lenalidomide when given together with cytarabine and idarubicin in treating patients with acute myeloid leukemia. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cytarabine and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cytarabine and idarubicin may kill more cancer cells.

研究概览

详细说明

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with conventional chemotherapy in two separate cohorts of patients with 1) relapsed or refractory acute myeloid leukemia (AML) and 2) age >= 60 with untreated AML and recommend starting doses for phase II studies of this combination of agents.

SECONDARY OBJECTIVES:

I. To define the qualitative and quantitative toxicities of these combinations of agents in regard to organ specificity, time course, predictability, and reversibility.

II. To document the therapeutic response of these combinations of agents in patients with poor risk AML.

III. To conduct pharmacodynamic studies to investigate the potential mechanism of lenalidomide activity in this trial.

OUTLINE: This is a dose-escalation study of lenalidomide.

INDUCTION:

COHORT I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, cytarabine intravenously (IV) continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.

COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.

Patients with residual disease on day 18 undergo a second course of induction therapy.

CONSOLIDATION:

COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

研究类型

介入性

注册 (实际的)

61

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

    • Ohio
      • Columbus、Ohio、美国、43210
        • Ohio State University Comprehensive Cancer Center

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 至 64年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Cohort 1: Patients must be age >= 18 and < 65 with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS); high risk MDS is defined as international prognosis scoring system (IPSS) score of 1.5 or higher; eligible patients will have a score of 1.5 or higher at any time from diagnosis to screening

    • Cohort 2: Patients must be age >= 18 with previously untreated AML; favorable risk AML patients < 60 years of age are excluded; these are defined as core binding factor (CBF) AML patients and characterized by cytogenetic or molecular evidence of CBF leukemia; untreated AML patients < 60 years of age must be negative on screening for CBF leukemia by cytogenetic or molecular analysis (Note: Prior therapy for MDS is permitted)
  • Patients with secondary AML or therapy-related disease (transformed [t]-AML/MDS) are eligible
  • If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin < 2.0 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper limit of normal
  • Creatinine < 2.0 mg/dL AND creatinine clearance (calculated) >= 50 mL/min
  • Left ventricular ejection fraction (LVEF) >= 40%
  • Patients who have previously received lenalidomide, idarubicin, and/or cytarabine are eligible provided that the combination of the 3 agents has never before been administered, and that no lenalidomide has been administered for at least 6 months
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a minimum sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; these methods of birth control must be used for the duration of study participation and for 28 days after lenalidomide discontinuation; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Ability to understand and willingness to sign the written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who have taken lenalidomide within the last 6 months
  • Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
  • Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
  • Patients with history of medically serious allergic reactions or non-hematologic toxicities attributed to the agents in this trial such as lenalidomide or thalidomide or compounds of similar chemical or biologic composition that are not easily managed, or patients with a history of cerebellar toxicity to cytarabine
  • Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled
  • Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Pregnant women or women who are breastfeeding; additional pregnancy testing before, during, and after lenalidomide treatment is required, as well as requirements for contraception before, during, and after lenalidomide treatment
  • Patients with advanced malignant solid tumors are excluded; patients with active additional hematologic malignancies are excluded
  • Patients with a history of neurologic toxicity with cytarabine are excluded
  • As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control
  • Known human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in HIV + patients once safety of the combination has been demonstrated

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:Treatment (lenalidomide, cytarabine, idarubicin)

INDUCTION:

COHORT I: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.

COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.

Patients with residual disease on day 18 undergo a second course of induction therapy.

CONSOLIDATION:

COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

相关研究
相关研究
其他名称:
  • 药理学研究
鉴于IV
其他名称:
  • CHX-3311
  • U-19920
给定采购订单
其他名称:
  • CC-5013
  • IMiD-1
  • CC5013
  • 疾控中心 501
鉴于IV
其他名称:
  • 伊霉素
  • IMI-30
  • SC-33428
  • 扎韦多斯

研究衡量的是什么?

主要结果指标

结果测量
大体时间
MTD of lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
大体时间:28 days
28 days

次要结果测量

结果测量
大体时间
Qualitative and quantitative toxicities, graded using NCI CTCAE version 4.0
大体时间:Up to 30 days post-treatment
Up to 30 days post-treatment
Therapeutic response, assessed using International Working Group criteria
大体时间:Up to 30 days post-treatment
Up to 30 days post-treatment
Pharmacodynamic studies, including micro-ribonucleic acid (miRNA)-181 family and target gene expression, CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) expression, and genes involved in erythroid differentiation
大体时间:Baseline, day 5, and day 28
Baseline, day 5, and day 28

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。

调查人员

  • 首席研究员:William Blum、Ohio State University Comprehensive 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。

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

2010年5月1日

初级完成 (实际的)

2014年1月1日

研究完成 (实际的)

2014年1月1日

研究注册日期

首次提交

2010年5月26日

首先提交符合 QC 标准的

2010年5月26日

首次发布 (估计)

2010年5月28日

研究记录更新

最后更新发布 (估计)

2014年12月23日

上次提交的符合 QC 标准的更新

2014年12月22日

最后验证

2014年11月1日

更多信息

与本研究相关的术语

其他研究编号

  • NCI-2011-01375 (注册表标识符:CTRP (Clinical Trial Reporting Program))
  • P30CA016058 (美国 NIH 拨款/合同)
  • UM1CA186712 (美国 NIH 拨款/合同)
  • 8455 (其他标识符:CTEP)
  • U01CA076576 (美国 NIH 拨款/合同)
  • OSU-10016
  • CDR0000673883
  • OSU 10016 (其他标识符:Ohio State University Comprehensive Cancer Center)

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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