Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of Dasatinib (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. Of the dose levels studied, to determine the maximum tolerated dose of dasatinib when given in combination with cytarabine and idarubicin for treatment of high risk acute myeloid leukemia (AML). (Phase I)
II. To determine the anti-tumor activity of dasatinib when given in combination with cytarabine and idarubicin, as assessed by complete remission rate (CR) and remission duration. (Phase II)
SECONDARY OBJECTIVES:
I. To document CR and survival outcomes (overall, event-free). (Phase I)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients diagnosed with AML meeting one of the following criteria:
- •Newly diagnosed, age 60 and older
- •High risk cytogenetics and molecular abnormalities (National Comprehensive Cancer Network [NCCN] criteria)
- •Relapsed or refractory to prior chemotherapy
- •Secondary AML
- •Any prior chemotherapy must have been completed >= 2 weeks prior to day 1 of study treatment and the participant must have recovered to eligibility levels from prior toxicity
- •Only one prior regimen is allowed for relapsed AML patients; note one prior regimen is defined as follows:
- •Induction chemotherapy followed by consolidation is considered one regimen
- •Induction chemotherapy followed by re-induction in case of persistent disease followed by consolidation is considered one regimen
- •Hydroxyurea is allowed prior to day 1 of study treatment to keep white blood cell (WBC) below 20 K
- •Karnofsky performance status >= 60%
- •Total bilirubin < 1.5 x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- •Creatinine < 1.5 x institutional upper limit or normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 x institutional upper limit of normal
- •Ejection fraction (EF) >= 45%
- •Ability to understand and sign a written informed consent document
- •Patients should not be receiving any other investigational agents
排除标准
- •Patients with clinically significant illness which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, immune deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection, active hepatitis B, active hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias; or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients with additional (other than AML) currently active primary malignancy other than curatively treated carcinoma in situ (CIS) of the cervix, or basal or squamous cell carcinoma of the skin; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy and disease free from prior malignancies for > 2 years
- •Patients with active central nervous system (CNS) disease
- •Patients with Chronic Myelogenous Leukemia (CML) in Myeloid blasts crisis
- •Active infections, including opportunistic infections
- •Women of childbearing potential (WOCBP) who have a positive serum pregnancy test within 14 days of the first administration of oral dasatinib
研究组 & 干预措施
Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: cytarabine (Drug)
Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: idarubicin (Drug)
Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: dasatinib (Drug)
Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: cytarabine (Drug)
Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: idarubicin (Drug)
Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: dasatinib (Drug)
Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum Tolerated Dose of Dasatinib (Phase I)
时间窗: From the first dose of Dasatinib through the DLT observation period (Day +28)
Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Complete Remission Rate (Phase II)
时间窗: From the first cycle up to two years
Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.
次要结局
- Event-free Survival (Phase II)(Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to two years.)
- Overall Survival (Phase II)(Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years)