Phase I Trial of R115777 (NSC 702818) in Relapsed, Refractory or High Risk Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- MTD defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing dose limiting toxicity (DLT) assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
研究概览
简要总结
Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase I trial is studying the side effects and best dose of tipifarnib in treating patients with relapsed or refractory acute myeloid leukemia
详细描述
PRIMARY OBJECTIVES:
I. To define the maximum tolerated dose (MTD) of R115777 (tipifarnib) in patients with relapsed, refractory, or high risk myeloid leukemias treated according to this regimen.
II. To assess the toxicity and preliminary assessment of efficacy of R115777 in patients with relapsed, refractory, or high risk myeloid leukemias.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with acute myeloid leukemia (AML), excluding the M3 subtype (acute promyelocytic leukemia), that are not likely to respond to conventional therapy, including:
- •Relapsed or refractory AML after one to three prior induction regimens (not counting consolidation therapies while in CR, such as autologous transplant),
- •Newly diagnosed AML in patients up to age-70 with poor risk features (unfavorable cytogenetics or findings suggestive of prior myelodysplasia) not fit for standard induction therapy, and
- •Newly diagnosed AML patients age 70 - 75 not fit for standard therapy (without history of prior myelodysplastic syndrome [MDS])
- •Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice
- •Patients with active central nervous system (CNS) leukemia are NOT eligible
- •Performance status of 60% or greater by the Karnofsky scale
- •If induction chemotherapy has been attempted, a minimum of 4 weeks must have elapsed since the completion of prior chemotherapy in order to be eligible for this study; hydroxyurea for control of blasts is not counted as chemotherapy, and may be given up until 24 hours before starting R115777
- •Patients may have had prior autologous transplant; they must be at least 100 days post transplant, and have had recovery of their counts with ANC > 1000 and platelets greater than 100K at some point post transplant, and be without active CMV or fungal disease
- •Patients may have received prior radiation therapy as part of a transplant conditioning regimen; radiotherapy must have been completed at least 100 days prior to starting on R115777
- •There are no minimum hematological parameter requirements prior to the first two cycles of R115777, as patients with AML and MDS are understood to have low ANC and platelet counts when the disease is active; however, patients with WBC greater than 30,000 will receive hydroxyurea to reduce WBC to below 30,000 at which point they may begin treatment with R115777
- •A pretreatment calculated creatinine clearance (absolute value) of >= 60 ml/minute or serum creatinine of < 1.5 x upper limit of normal is required
- •Serum bilirubin =< 2.0 mg/dl
- •SGOT and SGPT =< 2.5 times the institutional upper limits of normal
- •Any condition causing inability to swallow pills given by mouth will render patients ineligible for the trial
- •There must be no plans for the patient to receive concurrent hormonal, biologic, or radiation therapy
- •Patients eligible, at the time of starting the drug, for curative therapeutic approaches (such as allogeneic transplant) are not eligible for the trial; however, patients who achieve CR or PR as a result of R115777 may go on to allogeneic transplant
- •Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- •Prior to the first patient registration, the notification of institutional review board approval for this study must be provided to the Data Coordinating Center at City of Hope
- •Antacids are allowed but must not be taken concurrently with R115777; (there must be at least 2 hours between antacid intake and R115777 dosing)
- •Pregnant or lactating women are excluded from this trial; all patients of child-bearing potential, both male and female, must be advised to practice adequate contraception; premenopausal women must have a negative pregnancy test prior to entry on this study
排除标准
- 未提供
研究组 & 干预措施
Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.
干预措施: tipifarnib (Drug)
Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.
干预措施: pharmacological study (Other)
Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing dose limiting toxicity (DLT) assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: 28 days
The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Duration of response
时间窗: Up to 6.5 years
Will be summarized with Kaplan-Meier plots.
Objective tumor response
时间窗: Up to 6.5 years
Will be summarized at each dose level, and the number and percent responding combined across dose levels.
Survival
时间窗: From registration to time of death due to any cause, assessed up to 6.5 years
Will be summarized with Kaplan-Meier plots.
Time to treatment failure
时间窗: From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 6.5 years
Will be summarized with Kaplan-Meier plots.
次要结局
未报告次要终点