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Tipifarnib in Treating Young Patients With Refractory Leukemia

2012年3月14日更新者：National Institutes of Health Clinical Center (CC)

A Phase I Trial and Pharmacokinetic Study of R115777 in Pediatric Patients With Refractory Leukemia

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of tipifarnib in treating young patients who have refractory leukemia.

研究概览

地位

完全的

条件

白血病

干预/治疗

药品：替比法尼

详细说明

OBJECTIVES:

Primary

Determine the maximum tolerated dose and toxicity profile of tipifarnib in pediatric patients with refractory leukemia.
Determine the pharmacokinetics of this drug in these patients.
Determine the toxicity profile of this drug in these patients.

Secondary

Analyze the gene expression profile of leukemic blasts from these patients before and after treatment with this drug.
Determine circulating levels of nerve growth factor and correlate these levels with clinical neurotoxicity from this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral tipifarnib every 12 hours on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. At least 9 additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 12-34 patients will be accrued for this study within 1-2 years.

研究类型

介入性

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

加拿大
- Ontario
  - Toronto、Ontario、加拿大、M5G 1X8
    - Hospital for Sick Children
- Quebec
  - Montreal、Quebec、加拿大、H3T 1C5
    - Hopital Sainte Justine
  - Montreal、Quebec、加拿大、H3G 1A4
    - Montreal Children's Hospital at McGill University Health Center
澳大利亚
- Victoria
  - Parkville、Victoria、澳大利亚、3052
    - Royal Children's Hospital
- Western Australia
  - Perth、Western Australia、澳大利亚、6001
    - Princess Margaret Hospital for Children
美国
- Arkansas
  - Little Rock、Arkansas、美国、72205
    - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
- California
  - Duarte、California、美国、91010-3000
    - City of Hope Comprehensive Cancer Center
  - La Jolla、California、美国、92093-0658
    - Rebecca and John Moores UCSD Cancer Center
  - Los Angeles、California、美国、90095-1781
    - Jonsson Comprehensive Cancer Center, UCLA
  - Los Angeles、California、美国、90027-0700
    - Children's Hospital Los Angeles
  - Orange、California、美国、92868
    - Children's Hospital of Orange County
  - San Francisco、California、美国、94143
    - UCSF Comprehensive Cancer Center
  - Stanford、California、美国、94305-5208
    - Stanford Cancer Center at Stanford University Medical Center
- District of Columbia
  - Washington、District of Columbia、美国、20010-2970
    - Children's National Medical Center
- Florida
  - Gainesville、Florida、美国、32610-0296
    - Shands Cancer Center at the University of Florida Health Science Center
- Georgia
  - Atlanta、Georgia、美国、30342
    - AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
  - Augusta、Georgia、美国、30912-4000
    - MBCCOP-Medical College of Georgia Cancer Center
- Illinois
  - Chicago、Illinois、美国、60614
    - Children's Memorial Hospital - Chicago
- Indiana
  - Indianapolis、Indiana、美国、46202-5225
    - Riley Children Cancer Center at Riley Hospital for Children
- Kansas
  - Kansas City、Kansas、美国、66160-7357
    - Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
- Louisiana
  - New Orleans、Louisiana、美国、70112
    - MBCCOP - LSU Health Sciences Center
- Maryland
  - Baltimore、Maryland、美国、21231-7223
    - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  - Bethesda、Maryland、美国、20892-1182
    - Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
- Massachusetts
  - Boston、Massachusetts、美国、02115
    - Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  - Boston、Massachusetts、美国、02111
    - Floating Hospital for Children
- Michigan
  - Ann Arbor、Michigan、美国、48109-0914
    - University of Michigan Comprehensive Cancer Center
  - Detroit、Michigan、美国、48201
    - Children's Hospital of Michigan
- Minnesota
  - Minneapolis、Minnesota、美国、55455
    - University of Minnesota Cancer Center
  - Rochester、Minnesota、美国、55905
    - Mayo Clinic Cancer Center
- Mississippi
  - Jackson、Mississippi、美国、39216-4505
    - University of Mississippi Medical Center
- Missouri
  - Kansas City、Missouri、美国、64108
    - Children's Mercy Hospital
  - Saint Louis、Missouri、美国、63110
    - St. Louis Children's Hospital
  - Saint Louis、Missouri、美国、63104
    - Cardinal Glennon Children's Hospital
- New Jersey
  - Hackensack、New Jersey、美国、07601
    - Cancer Center at Hackensack University Medical Center
  - New Brunswick、New Jersey、美国、08901
    - Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
- New York
  - New York、New York、美国、10021
    - Memorial Sloan-Kettering Cancer Center
  - New York、New York、美国、10016
    - NYU School of Medicine's Kaplan Comprehensive Cancer Center
  - New York、New York、美国、10032
    - Herbert Irving Comprehensive Cancer Center at Columbia University
  - Syracuse、New York、美国、13210
    - SUNY Upstate Medical University Hospital
- North Carolina
  - Durham、North Carolina、美国、27710
    - Duke Comprehensive Cancer Center
- Ohio
  - Cincinnati、Ohio、美国、45229-3039
    - Cincinnati Children's Hospital Medical Center
  - Columbus、Ohio、美国、43205-2696
    - Columbus Children's Hospital
- Oklahoma
  - Oklahoma City、Oklahoma、美国、73126
    - Oklahoma University Medical Center
- Oregon
  - Portland、Oregon、美国、97225
    - CCOP - Columbia River Oncology Program
- Pennsylvania
  - Philadelphia、Pennsylvania、美国、19104-4318
    - Children's Hospital of Philadelphia
  - Pittsburgh、Pennsylvania、美国、15213-2583
    - Children's Hospital of Pittsburgh
- South Carolina
  - Charleston、South Carolina、美国、29425-0721
    - Hollings Cancer Center at Medical University of South Carolina
- Tennessee
  - Memphis、Tennessee、美国、38105-2794
    - St. Jude Children's Research Hospital
  - Nashville、Tennessee、美国、37232-6310
    - Vanderbilt Children's Hospital
- Texas
  - Dallas、Texas、美国、75390-9063
    - Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
  - Fort Worth、Texas、美国、76104
    - Cook Children's Medical Center - Fort Worth
  - Houston、Texas、美国、77030-4009
    - University of Texas - MD Anderson Cancer Center
  - Houston、Texas、美国、77030-2399
    - Texas Children's Cancer Center
  - San Antonio、Texas、美国、78207
    - University of Texas Health Science Center at San Antonio
  - San Antonio、Texas、美国、78229-3900
    - MBCCOP - South Texas Pediatrics
  - Temple、Texas、美国、76508
    - CCOP - Scott and White Hospital
- Utah
  - Salt Lake City、Utah、美国、84112
    - Huntsman Cancer Institute
- Washington
  - Seattle、Washington、美国、98105
    - Children's Hospital and Regional Medical Center - Seattle
- Wisconsin
  - Madison、Wisconsin、美国、53792-6164
    - University of Wisconsin Comprehensive Cancer Center
  - Marshfield、Wisconsin、美国、54449
    - CCOP - Marshfield Clinic Research Foundation
  - Milwaukee、Wisconsin、美国、53226
    - Midwest Children's 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

不超过 21年 (孩子、成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

DISEASE CHARACTERISTICS:

Histologically confirmed acute lymphoblastic leukemia, acute nonlymphoblastic leukemia, juvenile myelomonocytic leukemia (JMML), or chronic myelogenous leukemia (CML) in blast crisis
- Refractory to standard curative therapy
- Acute promyelocytic leukemia refractory to tretinoin and arsenic trioxide
- Philadelphia chromosome-positive CML refractory to imatinib mesylate
Greater than 25% blasts in bone marrow (M3 bone marrow) except for patients with JMML
Active extramedullary disease allowed
No active leptomeningeal leukemia

PATIENT CHARACTERISTICS:

Age:

21 and under

Performance status:

Karnofsky 50-100% (over 10 years of age)
Lansky 50-100% (10 years of age and under)

Life expectancy:

Not specified

Hematopoietic:

Not required to be normal

Hepatic:

Bilirubin normal
SGPT and SGOT normal
No significant hepatic dysfunction
No grade 3 or 4 liver function test results within the past month

Renal:

Creatinine normal OR
Creatinine clearance at least 60 mL/min
No significant renal dysfunction

Cardiovascular:

No significant cardiac dysfunction

Pulmonary:

No significant pulmonary dysfunction

Neurologic:

No history of grand mal seizures grade 3 or greater except febrile seizures
No persistent sensory or motor neuropathy greater than grade 2

Other:

No clinically significant unrelated systemic illness
No serious infection
No organ dysfunction that would preclude study participation
No requirement for total parenteral nutrition
No known allergy to azoles (e.g., clotrimazole, fluconazole, ketoconazole, voriconazole)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior colony-stimulating factor therapy (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa
At least 3 months since prior myeloablative therapy followed by bone marrow or stem cell transplantation
No concurrent immunotherapy
No concurrent GM-CSF or interleukin-11

Chemotherapy:

At least 2 weeks since prior chemotherapy
No concurrent intrathecal chemotherapy
No other concurrent chemotherapy

Endocrine therapy:

At least 1 week since prior corticosteroids
No concurrent corticosteroids (except for acute allergic reaction)

Radiotherapy:

At least 4 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery:

Not specified

Other:

Recovered from nonhematologic toxicity of all prior therapy
At least 1 week since prior retinoids
No antacids (magnesium- or aluminum-containing formulations) within 2 hours of study drug
No other concurrent investigational agents
No concurrent retinoids
No concurrent anticonvulsants

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
屏蔽：无（打开标签）

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

National Institutes of Health Clinical Center (CC)

合作者

National Cancer Institute (NCI)

Children's Oncology Group

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。

一般刊物

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

2001年6月1日

研究完成 (实际的)

2005年3月1日

研究注册日期

首次提交

2001年8月10日

首先提交符合 QC 标准的

2003年1月26日

首次发布 (估计)

2003年1月27日

研究记录更新

最后更新发布 (估计)

2012年3月15日

上次提交的符合 QC 标准的更新

2012年3月14日

最后验证

2012年3月1日

白血病的临床试验

Shenzhen Second People's Hospital

招聘中

中国 CML 患者停用 TKI (TFR_china)

白血病 | 骨髓的 | 慢性的 | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | 积极的

中国