A Phase 2 Study of AZD6244 in Relapsed or Refractory AML
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Response Rate for Subjects Without FLT3 ITD Mutation
研究概览
简要总结
This phase II clinical trial is studying how well selumetinib works in treating patients with recurrent or refractory acute myeloid leukemia. Selumetinib may stop the growth of cancer by blocking some of the enzymes needed for cell growth
详细描述
PRIMARY OBJECTIVES:
I. To determine the response rate (includes complete response-CR, complete response with incomplete count recovery CRi, partial response-PR, and minor response-MR) to AZD6244 (selumetinib).
SECONDARY OBJECTIVES:
I. To determine the effects of AZD6244 in AML samples on p-ERK and evaluate the potential utility of p-ERK inhibition as a surrogate marker of biologic activity.
II. To correlate the effects of AZD6244 with the presence (or absence) of mutated RAS or FLT-3 at baseline.
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
- •Histologically or cytologically confirmed diagnosis of 1 of the following:
- •Relapsed or refractory acute myeloid leukemia (AML)
- •Secondary AML including AML arising from antecedent hematologic diseases (e.g., myelodysplastic syndrome, myeloproliferative disorders, or therapy-related AML)
- •Elderly patients ≥ 60 years of age, previously untreated, and who are not candidates for or have refused standard chemotherapy are eligible for this trial
- •Patients with relapsed acute promyelocytic leukemia (APL) who are FLT3+ and have failed both tretinoin and arsenic therapy are eligible for this trial
- •No known active CNS disease
- •ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- •Total bilirubin ≤ 2 mg/dL (unless due to disease, hemolysis, or Gilbert disease)
- •In patients with associated hemolysis or Gilbert disease, a bilirubin of > 2 mg/dL is allowed as a result of predominantly unconjugated hyperbilirubinemia
- •AST/ALT < 3 times upper limit of normal
- •Creatinine < 2 mg/dL
- •Baseline pulse oximetry > 92%
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception prior to, during, and for 4 weeks (16 week for males) after completion of study treatment
- •Recovered from prior therapy
- •At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- •Hydroxyurea may be administered for the first 7 days of therapy in patients with rapidly rising white count (WBC > 20 K/μL)
- •At least 4 weeks since prior investigational agents
- •No prior MEK inhibitors
- •No concurrent medication that can prolong the QT interval
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
- •QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, or family history of long QT interval syndrome), including New York Heart Association class III or IV heart failure
- •Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situations that would limit compliance with study requirements
研究组 & 干预措施
Treatment (selumetinib)
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: selumetinib (Drug)
结局指标
主要结局
Response Rate for Subjects Without FLT3 ITD Mutation
时间窗: Up to 52 weeks
Responses were defined using standard criteria developed by an International Working Group. \[Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.\] In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).
次要结局
- Proportion of Subjects With Baseline p-ERK Activation(baseline (0 weeks))
- Proportion of Subjects With NRAS Mutation(baseline (0 weeks))
- Proportion of Subjects With KRAS Mutation(baseline (0 weeks))
- Proportion of Subjects With FLT3 ITD Mutation(baseline (0 weeks))
- Proportion of Subjects With KIT Mutation(baseline (0 weeks))