Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
研究概览
地位
条件
- 继发性急性髓性白血病
- 未经治疗的成人急性髓性白血病
- 成人急性单核细胞白血病
- 成人急性单核细胞白血病
- 成人急性髓性白血病伴 Inv(16)(p13.1q22); CBFB-MYH11
- 成熟的成人急性髓性白血病
- 成人急性髓性白血病伴微小分化
- 成人急性髓系白血病伴 t(16;16)(p13.1;q22); CBFB-MYH11
- 未成熟的成人急性髓性白血病
- 成人急性粒单核细胞白血病
- 烷化剂相关的急性髓性白血病
- 成人急性巨核细胞白血病
- 成人红白血病
- 成人纯红细胞白血病
- 成人急性髓系白血病伴 t(9;11)(p22;q23); MLLT3-MLL
- 成人急性髓性白血病伴 t(8;21)(q22;q22); RUNX1-RUNX1T1
干预/治疗
详细说明
PRIMARY OBJECTIVES:
I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.
SECONDARY OBJECTIVES:
I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.
III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.
OUTLINE: This is a multicenter study.
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.
After completion of study therapy, patients are followed up every 30 days.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Florida
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Tampa、Florida、美国、33612
- Moffitt Cancer Center
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Georgia
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Atlanta、Georgia、美国、30342
- Blood and Marrow Transplant Group of Georgia
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Atlanta、Georgia、美国、30322
- Emory University/Winship Cancer Institute
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Maryland
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Baltimore、Maryland、美国、21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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New York
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New York、New York、美国、10065
- Memorial Sloan-Kettering Cancer Center
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New York、New York、美国、10065
- Weill Medical College of Cornell University
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North Carolina
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Chapel Hill、North Carolina、美国、27599
- University of North Carolina
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Previously untreated acute myeloid leukemia (AML) (de novo or secondary)
- No diagnosis of acute promyelocytic leukemia (APL)
- Deemed unsuitable for or refuses standard induction chemotherapy
- RASGRP1:APTX ratio >= 5, through bone marrow screening
- No patients with known leukemic involvement of the central nervous system
- ECOG performance status =< 2
- No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
- Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)
- Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
- ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
- 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
- No symptomatic neuropathy of grade 2 or worse
- No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
- No 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
- Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy AND with a CD4 cell count >= 400/mm^3 are eligible
- No other concurrent cytotoxic or biologic antileukemic therapy
- No patients who are receiving any other investigational agents
Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated
- If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777
学习计划
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 (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21.
Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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相关研究
给定采购订单
其他名称:
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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 |
---|---|---|
Complete Remission (CR) Rate
大体时间:From first treatment through follow up period, an expected average of 12 months
|
Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.
AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
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From first treatment through follow up period, an expected average of 12 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Median Overall Survival (OS)
大体时间:From first treatment through follow up period, an expected average of 12 months
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Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).
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From first treatment through follow up period, an expected average of 12 months
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Median 1-Year Survival Rate
大体时间:1 year
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Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.
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1 year
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Number of Participants With Relapse Free Survival
大体时间:7 months
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Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.
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7 months
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合作者和调查者
调查人员
- 首席研究员:Jeffrey Lancet、Moffitt Cancer Center
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
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
- NCI-2011-02589 (注册表标识符:CTRP (Clinical Trial Reporting Program))
- U01CA070095 (美国 NIH 拨款/合同)
- N01CM00071 (美国 NIH 拨款/合同)
- P30CA076292 (美国 NIH 拨款/合同)
- N01CM00100 (美国 NIH 拨款/合同)
- 16572
- CDR0000699713
- 8977 (其他标识符:CTEP)
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