A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 5
- 主要终点
- The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
研究概览
简要总结
This phase II trial is studying how well cediranib maleate works in treating patients with relapsed, refractory, or untreated acute myeloid leukemia or high-risk myelodysplastic syndrome. Cediranib maleate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the objective response rate in patients with relapsed, refractory, or untreated acute myeloid leukemia or high-risk myelodysplastic syndromes treated with AZD2171 (cediranib maleate).
SECONDARY OBJECTIVES:
I. Determine the toxicity of this drug in these patients. II. Determine the response duration, event-free survival, and overall survival of patients treated with this drug.
III. Determine the hematological response rate in patients treated with this drug.
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 acute myeloid leukemia (AML) ormyelodysplastic syndromes meeting 1 of the following criteria:
- •Relapsed AML meeting any of the following criteria:
- •Good-risk cytogenetics (inv[16], t[8;21], or t[15;17]) in second orgreater relapse
- •Patients with AML t(15;17) must have failed prior tretinoin and arsenic-containing regimens AND progressed orrelapsed within 12 months of therapy
- •In first or greater relapse
- •Resistant AML
- •Unable to achieve first complete remission after at least 2 inductionregimens
- •Untreated AML meeting any of the following criteria:
- •At least 60 years of age
- •Preceding MDS
- •International Prognosis Scoring System (IPSS) risk groupof intermediate-2 or higher
- •Patients with relapsed disease after allogeneic hematopoietic stem cell transplantation (HSCT) must be off allimmunosuppressive medications for at least 30 days and have no symptoms orsigns of graft-vs-host disease
- •No active CNS metastasis
- •Patients with clinical signs of CNS disease or a history of CNS diseasewithin the past 6 months are required to undergo lumbar puncture to excludeCNS involvement
- •No symptomatic leukostasis or requirement for leukapheresis
- •Not eligible for allogeneic HSCTAND no suitable donor at the time of study entry
- •Patients who areeligible for HSCT, informed of the option, and choose not to proceed to HSCTare allowed
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Bilirubin normal
- •AST and/or ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •No proteinuria ≥ 1+ on 2 consecutive urinalysis taken ≥ 1 week apart
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No HIV positivity
- •LVEF ≥ 45% by echocardiography
- •Mean QTc ≤ 500 msec (with Bazett's correction)
- •No other significant ECG abnormality
- •No history of familial long QT syndrome
- •No disseminated intravascular coagulation
- •No history of allergic reactions attributed to compounds of similar chemical orbiological composition to AZD2171
- •No concurrent uncontrolled illness, including, but not limited to, any of the following:
- •Hypertension
- •Thyroid disease
- •Ongoing or active infection
- •Symptomatic congestive heartfailure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •NYHA class III-IV heart disease
- •NYHA class II heart disease controlled with treatment allowed
- •Psychiatric illness or social situations that would limit study compliance
- •See Disease Characteristics
- •More than 4 weeks since prior chemotherapy (6 weeks fornitrosoureas or mitomycin C), radiotherapy, or major surgery and recovered
- •Hydroxyurea allowed to control peripheral blast count> 20,000/mcL prior to study entry and during the first 3 days of study therapy
- •More than 4 weeks since prior and no concurrent growth factor or other cytokine support
- •At least 30 days since prior investigational agents or participation in aninvestigational trial
- •No more than 3 prior courses of induction chemotherapy
- •Induction chemotherapyis defined as that intended to induce complete remission and given at a time thatthe patient has active disease
- •No concurrent CYP interactive medications
- 另有 3 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cediranib maleate (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
时间窗: At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cycles
Complete Response (CR) requires a repeat bone marrow with \< 5% myeloblasts, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Partial Response (PR) requires a bone marrow blast reduction of 50% or more, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Hematologic Improvement (HI) requires one of the following: 1. RBC transfusion independent participants are required to have \>1.5 g/dL increase in hemoglobin, 2. RBC transfusion-dependent participants are required to be transfusion independent, 3. A 100% increase, and an absolute increase over 500mm\^3 in Absolute Neutrophil Count, 4. Participants with a pretreatment platelet count over 20,000/mm3 require an absolute increase of 30,000/mm\^3 or more, 5. Participants with platelet count below 20,000/mm3 require an increase over 20,000/mm\^3 and by at least 100%.
次要结局
- Overall Survival(Every cycle during treatment and every 6 months for up to 2 years after completion of study treatment)
- Progression-free Survival(Every 3 courses during treatment and then at 3 months and every 6 months for up to 2 years after completion of study treatment)
- Duration of Response(Every 3 courses up to 26 courses)
- The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.(Continuously during treatment up to 26 courses)