Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Response rate
研究概览
简要总结
This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. 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 toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.
II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.
OUTLINE: This is a dose-escalation study.
Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
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
- •Patients must have histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria
- •By these criteria, FAB RA are split into:
- •Pure dyserythropoietic refractory anemia (PRA)
- •Refractory cytopenia with multilineage dysplasia (RCMD)
- •FAB RARS is split into:
- •Pure sideroblastic anemia (PSA)
- •Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)
- •FAB RAEB is split into:
- •RAEB I (< 10% BM blasts)
- •RAEB II (10-20% BM blasts)
- •Patients with CMMoL, and RAEBT by FAB classification will be included in the protocol
- •Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria
- •=< 2 prior therapies
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Life expectancy of greater than 12 weeks
- •Bilirubin =< 1.5mg %
- •Creatinine =< 1.5mg %
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles)
- •Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant
- •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
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with R
- •Growth factors other than filgrastim (G-CSF) are excluded; patients should be off excluded growth factors for 2 weeks
研究组 & 干预措施
Treatment (tipifarnib)
Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: tipifarnib (Drug)
Treatment (tipifarnib)
Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (tipifarnib)
Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Response rate
时间窗: Up to 8.5 years
Will be reported overall and by dose level.
MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria
时间窗: Up to 8.5 years
The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.
次要结局
- FTase inhibition(Up to 8.5 years)
- Accumulation of unfarnesylated lamin B1(Up to 8.5 years)
- Accumulation of RAS proteins(Up to 8.5 years)