A Phase II Study of the Farnesyltransferase Inhibitor ZARNESTRA (Tipifarnib, R115777, NSC #702818, IND #58,359) in Complete Remission Following Induction and/or Consolidation Chemotherapy in Adults With Poor-Risk Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplasia (MDS).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Disease-free survival
研究概览
简要总结
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating patients who have acute myeloid leukemia or myelodysplastic syndrome in first complete remission
详细描述
PRIMARY OBJECTIVES:
I. To determine the duration of disease-free survival (DFS) and overall survival (OS) when ZARNESTRA is administered after intensive induction and consolidation chemotherapy to adults with poor risk acute myelogenous leukemia (AML) or high-risk myelodysplasia (MDS) in first complete remission (CR).
SECONDARY OBJECTIVES:
I. To determine the tolerability and toxicities of ZARNESTRA when administered in a chronic dosing schedule over a 48 week period to adults in first CR following intensive cytotoxic chemotherapies.
OUTLINE: This is a multicenter study.
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
- •Pathological Confirmation of the Diagnosis of AML, MDS
- •PMNs >= 1,000/ul
- •Platelets >= 30,000/ul
- •Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported
- •ECOG Performance Status 0-2
- •Patients must be able to give informed consent
- •Female patients of childbearing age must have negative pregnancy test
- •AST, ALT and Alkaline Phosphatase =<2.5 x normal
- •Bilirubin =< 1.5 x normal
- •Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min
- •Left Ventricular Ejection Fraction >= 25%
- •Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics:
- •Antecedent Hematologic Disorder
- •AML Arising from MDS
- •Therapy-related AML
- •Age >= 60 (in absence of favorable cytogenetics)
- •Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair)
- •Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics)
- •High Risk MDS is defined by one or more of the following characteristics:
- •RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36
- •CMML with > 5% marrow blasts
- •Therapy-related MDS
排除标准
- •Any previous treatment with ZARNESTRA
- •Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial)
- •Acute promyelocytic (FAB M3) subtype
- •Presence of (8;21) translocation or inversion 16 genotype as sole abnormality
- •Eligible for curative allogeneic stem cell transplantation
- •Known allergy to imidazole drugs (e.g., ketoconazole, miconazole)
- •Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics
- •Active, Uncontrolled Infection
- •Disseminated Intravascular Coagulation
- •Active CNS Leukemia
- •Concomitant Chemotherapy, Radiation Therapy or Immunotherapy
- •Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant
研究组 & 干预措施
Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
干预措施: tipifarnib (Drug)
结局指标
主要结局
Disease-free survival
时间窗: 6 months
The trial is a success if greater than 45% of patients survive to 6 months. Comparing this to the null hypothesis of 25% survival, we have 84% power to detect this difference using an exact 2-sided binominal test of proportions for alpha of 0.10. This assumes no censoring occurs before 6 months.
次要结局
- Tolerability and toxicities of ZARNESTRA when administrated in a chronic dosing schedule over a 48-week period to adults in first CR following intensive cytotoxic chemotherapy(Up to 48 weeks)