A Phase 1, Open-label, Dose-escalation, Safety and Biomarker Prediction of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD) of Alvocidib
研究概览
简要总结
The purpose of this Phase I study is to determine the safety and tolerability including the maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML
详细描述
Primary Objective:
• To determine the safety and tolerability including the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML
Secondary Objectives:
- To observe patients for any evidence of antileukemic activity of alvocidib plus 7+3 using the 2017 ELN response criteria
- To establish the Recommended Phase 2 Dose (RP2D) for future studies with alvocidib in combination with 7+3
Exploratory Objective:
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for participation in the study, patients must meet all of the following inclusion criteria:
- •Be between the ages of ≥18 and ≤65 years
- •Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria with ≥20% bone marrow blasts based on histology or flow cytometry
- •Be newly diagnosed and previously untreated
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
- •Have a serum creatinine level ≤1.8 mg/dL
- •Have an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)
- •Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)
- •Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
- •Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of study drug.
- •Be able to comply with the requirements of the entire study.
- •Provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)
排除标准
- •Patients meeting any one of these exclusion criteria will be prohibited from participating in this study.
- •Received any previous treatment for AML
- •Diagnosed with APL-M3 or CBF-AML
- •Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.
- •Received >200 mg/m2 equivalents of daunorubicin
- •Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #3 above)
- •Have active central nervous system (CNS) leukemia
- •Have evidence of uncontrolled disseminated intravascular coagulation
- •Have an active, uncontrolled infection
- •Have other life-threatening illness
- •Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
- •Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
- •Are pregnant and/or nursing
研究组 & 干预措施
Alvocidib and Cytarabine/Daunorubicin
The starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.
干预措施: Alvocidib (Drug)
Alvocidib and Cytarabine/Daunorubicin
The starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.
干预措施: Cytarabine (Drug)
Alvocidib and Cytarabine/Daunorubicin
The starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.
干预措施: Daunorubicin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Alvocidib
时间窗: During the first cycle
Determine the safety and tolerability including the maximum tolerated dose (MTD) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) of Alvocidib
时间窗: During the first cycle
Determine the safety and tolerability including dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML
次要结局
- Antileukemic Activity of Alvocidib Plus 7+3 - Response to Treatment Based on 2017 ELN Response Criteria(Best response during duration of study)
- Recommended Phase 2 Dose (RP2D) of Alvocidib in Combination With 7+3(During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days)