Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 7
- 主要终点
- Complete Remission (CR) Rate
研究概览
简要总结
This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Tipifarnib (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Complete Remission (CR) Rate
时间窗: 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.
次要结局
- Median Overall Survival (OS)(From first treatment through follow up period, an expected average of 12 months)
- Median 1-Year Survival Rate(1 year)
- Number of Participants With Relapse Free Survival(7 months)