Phase I Study of Farnesyl Transferase Inhibitor BMS-214662 (NSC 710086) in Acute Leukemias, Myelodysplastic Syndromes (RAEB and RAEB-T) and Chronic Myeloid Leukemia in Blast Phase
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 dose preceding that at which 2 of 6 patients experience DLT assessed using NCI CTC version 2.0
研究概览
简要总结
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of BMS-214662 in treating patients who have acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and dose limiting toxicity of BMS-214662 in patients with acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase.
II. Determine any preliminary evidence of antileukemia activity of this drug in these patients.
OUTLINE: This is a dose escalation study.
Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have:
- •AML, ALL, or high-risk MDS (RAEB or RAEB-t) that has:
- •Not responded (no CR) to initial induction chemotherapy, or
- •Recurred after an initial CR of < 1 year, or
- •Recurred after an initial CR of > 1 year and failed to respond to an initial reinduction attempt, or
- •Recurred more than once, or
- •Chronic myeloid leukemia in myeloid blast phase
- •Patients with CML blast phase may receive BMS-214662 as their first therapy for blast phase or after failing other treatments for blast phase
- •Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen
- •Performance status of =< 0-2
- •Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of the hospital
- •Patients must have been off chemotherapy for the 4 weeks prior to entering this study and recovered from the toxic effects of that therapy; patients with evidence of rapidly progressive disease (i.e., absolute peripheral blood blast count >= 5 x 10^9/L and increasing by >= 1 x 10^9/L/24 hours) may receive treatment before 4 weeks from the previous treatment providing they have recovered from all toxic effects of that therapy; use of hydroxyurea on patients with rapidly proliferative disease is allowed up to 24 hours prior to the start of therapy
- •Bilirubin =< 1.5 mg/dL
- •Creatinine =< 1.5 mg/dL or creatinine clearance >= 60 mL/hr
- •Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible
排除标准
- •Pregnant and nursing females will be excluded; patients of childbearing potential should practice effective methods of contraception
- •Patients with prolonged QTc interval on EKG are excluded
研究组 & 干预措施
Treatment (BMS-214662)
Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
干预措施: BMS-214662 (Drug)
Treatment (BMS-214662)
Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
干预措施: pharmacological study (Other)
Treatment (BMS-214662)
Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD defined as the dose preceding that at which 2 of 6 patients experience DLT assessed using NCI CTC version 2.0
时间窗: 4 weeks
Non-parametric tests will be used to study the relationship between baseline and post-therapy values at different dose levels and times.
次要结局
未报告次要终点