A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
研究概览
简要总结
This phase I trial is studying the side effects and best dose of tipifarnib and bortezomib in treating patients with acute leukemia or chronic myelogenous leukemia in blast phase. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tipifarnib together with bortezomib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVE:
I. Determine the dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib in patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myeloid leukemia in blast phase.
SECONDARY OBJECTIVES:
I. Determine the effect of this regimen on farnesyltransferase and proteasome inhibition in peripheral blood mononuclear cells in these patients.
II. Determine the clinical efficacy of this regimen in these 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
- •Meets 1 of the following disease-specific criteria:
- •Relapsed disease after =< 2 prior chemotherapy regimens (consolidation therapy excluded)
- •Primary-induction failure
- •Previously untreated and deemed unfit for or refusing cytotoxic chemotherapy
- •No hyperleukocytosis (leukemic blasts >= 30,000/mm^3)
- •No acute promyelocytic leukemia (M3)
- •No active CNS leukemia
- •SGOT and SGPT =< 2 times upper limit of normal (ULN)
- •Bilirubin normal
- •Creatinine =< 1.5 times ULN
- •No uncontrolled hypertension, congestive heart failure, angina pectoris, or ventricular dysrhythmias
- •Not pregnant or nursing
- •Negative pregnancy test
- •No uncontrolled disseminated intravascular coagulation
- •Fertile patients must use effective contraception
- •Hormonal contraception must have been initiated ≥ 1 month prior to study entry
- •No active graft-vs-host disease
- •No active uncontrolled infection
- •No intrinsic impaired organ function
- •No known allergy to imidazole drugs
- •No neuropathy >= grade 1
- •No known hypersensitivity to bortezomib, tipifarnib, boron, or mannitol
- •No physical or psychiatric conditions that would preclude study participation, including poorly controlled psychosis
- •At least 48 hours since prior hydroxyurea
- •No prior tipifarnib, bortezomib, or investigational proteasomal inhibitors
- •No concurrent radiotherapy, chemotherapy, or immunotherapy
- •No concurrent enzyme-inducing antiepileptic medications (e.g., phenytoin, phenobarbital, or carbamazepine)
- •ECOG performance status 0-2
- •LVEF >= 40%
- •Pathologically confirmed diagnosis of 1 of the following:
- •Acute myeloid leukemia
- •Acute lymphoblastic leukemia
- •Chronic myelogenous leukemia in blast phase
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients will receive an infusion of bortezomib twice a week for 2 weeks. They will also receive tipifarnib by mouth twice a day for 2 weeks.
干预措施: Bortezomib (Drug)
Arm I
Patients will receive an infusion of bortezomib twice a week for 2 weeks. They will also receive tipifarnib by mouth twice a day for 2 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I
Patients will receive an infusion of bortezomib twice a week for 2 weeks. They will also receive tipifarnib by mouth twice a day for 2 weeks.
干预措施: Tipifarnib (Drug)
结局指标
主要结局
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
时间窗: 21 days
次要结局
- Clinical efficacy (response rate) evaluated using the revised International Working Group Criteria (IWG) for AML(Up to 3 years)
- Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells(Day 15)
- Changes in apoptotic protein expression (Bim, Bax, AKT)(Baseline and day 8)