A Phase I Study Of XL119 In Patients With Relapsed Or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes, Acute Lymphocytic Leukemia, Or Chronic Myeloid Leukemia In Blastic-Phase
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of becatecarin
研究概览
简要总结
This phase I trial is studying the side effects and best dose of rebeccamycin analog in treating patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blast phase. Drugs used in chemotherapy, such as rebeccamycin analog, work in different ways to stop cancer cells from dividing so they stop growing or die
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of rebeccamycin analogue (XL119) in patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blastic phase.
OUTLINE: This is a dose-escalation study.
Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 1 additional course beyond CR. Patients achieving a partial response (PR) or hematologic improvement (HI) receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of 1 of the following:
- •Acute myeloid leukemia
- •Myelodysplastic syndromes, including 1 of the following:
- •Refractory anemia with excess blasts (RAEB)
- •RAEB in transformation
- •Chronic myelomonocytic leukemia in transformation with ≥ 10% peripheral blood or bone marrow blasts
- •Acute lymphoblastic leukemia
- •Chronic myelogenous leukemia in blastic phase
- •Relapsed or refractory disease, defined as 1 of the following:
- •Failed to achieve a complete response (CR) to a standard induction regimen
- •Relapsed after achieving a CR
- •Failed last cytotoxic regimen before study entry
- •No alternate, potentially curative option available
- •No known CNS disease
- •Performance status - ECOG 0-2
- •SGOT and SGPT normal
- •Bilirubin normal
- •Creatinine normal
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV-positive patients with normal CD4 count and without AIDS-defining disease allowed
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to rebeccamycin analogue (XL119)
- •No concurrent uncontrolled illness
- •No active or ongoing infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No prior allogeneic stem cell transplantation
- •No concurrent prophylactic hematopoietic colony-stimulating factors (CSF)
- •No epoetin alfa or hematopoietic CSF during course 1 of study therapy
- •More than 7 days since prior cytotoxic chemotherapy except for hydroxyurea
- •More than 7 days since prior radiotherapy
- •Recovered from all prior therapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer agents or therapies
- •No other concurrent antileukemic agents or therapies
- •No other concurrent investigational agents or therapies
- •No other concurrent cytotoxic agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (becatecarin)
Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: becatecarin (Drug)
Treatment (becatecarin)
Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose of becatecarin
时间窗: 21 days
Graded using the NCI CTCAE version 3.0.
次要结局
- Survival(From date of first study drug administration to the date of death of the patients, assessed up to 3 years)
- Time to progression(From the date of first study drug administration to the date that the patient is withdrawn because of clinical or radiographic progressive disease, or death from any cause, assessed up to 3 years)
- Time to treatment failure(From the date of first study drug administration to the date of withdrawal from the study for any reason other than study closure, assessed up to 3 years)
- Duration of response(From the date of first objective response to the date of progression, assessed up to 3 years)
- Time to response(From the date of first study drug administration until the first objective documentation of response, assessed up to 3 years)