A Phase I, Open-labeled Multicenter Study to Determine Pharmacokinetics, Safety, Tolerability and Efficacy of Uproleselan in Combination With Chemotherapy in Chinese Patients With Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Peak plasma concentration (Cmax)
研究概览
简要总结
This study will evaluate the safety and tolerability of uproleselan(GMI-1271), a specific E-selectin antagonist, and characterize the pharmacokinetic (PK) profile of uproleselan, in combination with chemotherapy to treat Chinese relapsed/refractory AML patients.
详细描述
This study is a multicenter open-labelled study conducted in subjects with relapsed or refractory AML in China. The study includes the following phases: screening phase, induction phase, consolidation phase baseline, consolidation phase and follow-up period.
Screening phase:
This study will enroll 12 subjects, who are 18 to 60 years (inclusive) at the time of signing the Informed Consent Form (ICF), and with the diagnosis as relapsed or refractory AML. Screening is conducted 21 days to 2 days before administration, and signed ICF by the subject must be obtained before screening.
Baseline period:
The baseline period is 1 day before study drug administration.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years and ≤60 years in age
- •AML (including secondary AML) diagnosed as per WHO standards (2008).
- •For refractory AML, only cytarabine/daunorubicin(or Idarubicin) as can be applied repeatedly(maximal twice) as induction, no other chemotherapy are allowed to be applied Venatoclax /hypomethylation drug [HMA] can be used before and after chemotherapy.
- •For relapse AML, it must be the first or second relapse, and remain untreated.
- •Certain regimens (Venatoclax/HMA, Venetoclax/LDAC, HMA single agent) and FLT3 inhibitors, tyrosine kinase inhibitors, IDH1/IDH2 inhibitors or similar targeted inhibitors used alone are not considered cytotoxic chemotherapy are allowed.
- •ECOG performance status score is 0 to
- •Stable hemodynamics and good organ function.
排除标准
- •Patients with acute promyelocytic leukemia, acute leukemia of ambiguous lineage (biphenotypic leukemia), chronic myeloid leukemia with myeloid blast crisis, or secondary refractory AML.
- •Active signs or symptoms of CNS involvement by malignancy.
- •Stem cell transplantation ≤4 months prior to dosing.
- •Any immunotherapy or radiotherapy therapy within 28 days of dosing; any other experimental therapy or chemotherapy within 14 days of dosing.
- •Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing.
- •Inadequate organ function.
- •Abnormal liver function.
- •Known active infection with hepatitis A, B, or C, or human immunodeficiency virus.
- •Moderate kidney dysfunction (glomerular filtration rate <45 mL/min).
- •Uncontrolled acute life-threatening bacterial, viral, or fungal infection.
- •Clinically significant cardiovascular disease.
- •Major surgery within 4 weeks of dosing.
研究组 & 干预措施
A Phase I, open-labeled multicenter study
Uproleselan in combination with mitoxantrone, etoposide and cytarabine (MEC)
干预措施: Uproleselan (Drug)
结局指标
主要结局
Peak plasma concentration (Cmax)
时间窗: 14 days
To assess the pharmacokinetic profile in patients with relapsed/refractory AML.
Peak plasma concentration (Tmax)
时间窗: 14 days
To assess the pharmacokinetic profile in patients with relapsed/refractory AML.
Area under the plasma concentration-time curve from time zero to 12 hours (AUC0-12)
时间窗: 14 days
To assess the pharmacokinetic profile in patients with relapsed/refractory AML.
The area under the plasma concentration-time curve (AUC0-t) from time zero to the last measurable time point
时间窗: 14 days
To assess the pharmacokinetic profile in patients with relapsed/refractory AML.
The Incidence of Adverse Events
时间窗: Up to 10 months
Number of participants with an AE.
The tolerance of participants with relapsed/refractory AML.
时间窗: Up to 10 months
Number of participants could tolerate the Uproleselan combined with chemotherapy.
次要结局
- OS(Up to 3 years)
- Remission rate (rate of CR, CR/CRi and CR/CRh)(Up to 60 days)
- CTCAE grade 3 and 4 oral mucositis(Up to 254 days)