PHASE I-II STUDY OF IDARUBICIN, CYTARABINE AND R115777 (TIPIFARNIB, ZARNESTRA; 702818; IND 58359), A FARNESYLTRANSFERASE INHIBITOR, IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIAS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Number of Participants With Complete Response
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of tipifarnib when given with idarubicin and cytarabine and to see how well it works in treating patients with newly diagnosed myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Tipifarnib (Zarnestra) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving idarubicin and cytarabine with tipifarnib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the tolerability of the combination of R115777 (Zarnestra™) and Idarubicin plus cytarabine by defining the DLT and MTD. (Phase I) II. To determine the efficacy of the combination of Idarubicin, cytarabine and ZARNESTRA in patients with high-risk MDS and AML. (Phase II)
OUTLINE: This is a dose-escalation study of tipifarnib. Patients are stratified according to age (< 50 versus ≥ 50) and, in patients ≥ 50 years of age, cytogenetics (diploid versus unfavorable).
INDUCTION THERAPY:
PHASE I: Patients receive cytarabine IV continuously on days 1-3 (or 1-4), idarubicin intravenous (IV) over 1 hour on days 1-3, and oral tipifarnib twice daily on days 1-21. Treatment repeats every 21 days 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
- 15 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) high risk MDS (defined as the presence of > 10% blasts)
- •Patients must be chemo-naïve, i.e. not have received any prior chemotherapy (except hydrea) for AML or MDS; they could have received transfusions, hematopoietic growth factors or vitamins; temporary measures such as pheresis or hydrea (0.5 to 5g daily for up to 3 days) are allowed
- •ECOG PS of 0-1 at screening
- •Creatinine =< 2 mg/dl
- •Total bilirubin =< 2 mg/dL, unless increase is due to hemolysis
- •Transaminases (SGPT) =< 2.5 x ULN
- •Ability to take oral medication
- •Ability to understand and provide signed informed consent
排除标准
- •Subjects with APL
- •Presence of active systemic infection
- •Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
- •Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study
- •Known allergy to imidazole drugs (such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, terconazole)
研究组 & 干预措施
Arm I
See Detailed Description
干预措施: cytarabine (Drug)
Arm I
See Detailed Description
干预措施: idarubicin (Drug)
Arm I
See Detailed Description
干预措施: tipifarnib (Drug)
结局指标
主要结局
Number of Participants With Complete Response
时间窗: 21 Day Cycle
Complete Response (CR) is required bone marrow blasts ≤5% and recovery of normal hematopoiesis with an absolute neutrophil count (ANC) of 1\*10\^9/L or more and platelet count of 100\*10\^9/L or more; and a complete response without platelets (CRp) is the same criteria as CR but with platelet counts from 20\*10\^9/L to less than 100\*10\^9/L.
次要结局
未报告次要终点