Phase I/II Study of Tipifarnib [Zarnestra, Farnesyltransferase Inhibitor R115777 (NSC 702818)] in Patients With Myeloproliferative Disorders
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- WBC response (complete response, defined as normalization of WBC count in patients with an elevated WBC count prior to treatment and partial response, defined as > 50% reduction in WBC count without normalization of WBC count)
研究概览
简要总结
This phase 1-2 trial studies the side effects and how well tipifarnib works in treating patients with chronic myeloid leukemia, chronic myelomonocytic leukemia, or undifferentiated myeloproliferative disorders. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
- To describe the toxicities of R115777 (tipifarnib) in adult patients with myeloproliferative disorders.
- To assess hematologic responses, including changes in white blood cell count and erythroid responses.
SECONDARY OBJECTIVES:
- To assess bone marrow cytogenetic responses to R115777.
- To analyze for the presence of neuroblastoma (N)/Kirsten rat sarcoma viral oncogene homolog (K-Ras) mutations in patient bone marrow samples.
- To analyze the effect of R115777 on Ras /DnaJ (Hsp40) homolog, subfamily A, member 1(HDJ-2) farnesylation in patient bone marrow/peripheral blood mononuclear cells.
- To analyze the effect of R115777 on mitogen-activated protein (MAP) kinase activation in patient bone marrow mononuclear cells.
- To perform colony forming unit granulocyte-macrophage (CFU-GM) cytotoxicity assays using patients' hematopoietic cells with R115777.
OUTLINE:
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment (tipifarnib)
Patients receive tipifarnib PO BID on days 1-21. Treatment repeats every 28 days for up to 4 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 days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Tipifarnib (Drug)
结局指标
主要结局
WBC response (complete response, defined as normalization of WBC count in patients with an elevated WBC count prior to treatment and partial response, defined as > 50% reduction in WBC count without normalization of WBC count)
时间窗: Up to 16 weeks
For all hematologic responses, the duration of response must be at least 2 months.
Erythroid response in non-transfusion dependent patients
时间窗: Up to 16 weeks
Major response is defined as a \> 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy. Minor response is defined as a \> 1.0 to \< 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy.
Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0
时间窗: Up to 16 weeks
Erythroid response in transfusion-dependent patients
时间窗: Up to 16 weeks
Major response is defined as transfusion-independent after 2 to 4 cycles of therapy or a \> 2.0 g/dL rise in hemoglobin without transfusion. Minor response is defined as \> 1 to \< 2.0 g/dL incremental rise in hemoglobin with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8-week pre-study period.
次要结局
- In vitro correlative studies (including N/K-Ras mutation analysis, N/K-Ras/HDJ-2 farnesylation, MAP kinase activation, and bone marrow CFU-GM cytotoxicity assays using tipifarnib with patients' hematopoietic cells)(Up to week 3 (course 4))
- Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML)(Up to 16 weeks)