A Single-arm, Open, Multicenter, Phase II Study to Investigator the Efficacy and Safety of HYML-122 and Cytarabine in Patients With FLT3 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- composite complete remission (CRc) rate
研究概览
简要总结
This is a single-arm, open, multicenter, phase 2 study to evaluate the efficacy, safety and pharmacokinetics of HYLM-122 in combination with cytarabine in Chinese subjects with FLT3 positive relapsed or refractory acute myeloid leukemia.
详细描述
This study will have two phases. Phase 1: the escalation phase is to establish the recommended phase 2 dose (RP2D) of HYML-122 given in combination with cytarabine.
Phase 2: the extension phase study will treat patients with FLT3 positive relapsed or refractory AML with HYML-122 in combination with cytarabine at the RP2D, and further evaluate efficacy and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
- •Males and/or females at least 18 years old when signing the informed consent form.
- •Histologically confirmed AML (defined using WHO criteria 2016) with one of the following: Refractory to at least 1 cycle of induction chemotherapy. Relapsed after achieving remission with a prior therapy.
- •Subject is positive for FLT3 mutation in bone marrow or blood after completion of the subject's last interventional treatment.
- •Eastern cooperative oncology group performance status (ECOG) ≤2 at screening.
- •Life expectancy of at least 3 months.
- •Women of childbearing potential have a negative pregnancy test at baseline and are willing to employ an effective method of contraception for the entire duration of study treatment and 6 months after the last dose.
排除标准
- •Known or suspected allergies to any of the investigational drug composition (HYML-122, lactose, hydroxypropyl cellulose, hyposubstituted hydroxypropyl cellulose, silicon dioxide, magnesium stearate, titanium dioxide and polyethylene glycol).
- •Medical history and surgical history excluded according to the protocol.
- •Any previous medical treatment history exclude from the protocol.
- •Abnormal laboratory results exclude from the protocol.
- •Combination of treatments and/or drugs required during the study period and cannot be discontinued that excluded from the protocol.
- •Alcohol abuse within 6 months prior to screening, defined as long-term drinking history, generally more than 5 years, equivalent to alcohol quantity ≥40g/d for men, ≥20g/d for women, or heavy drinking history within 2 weeks, equivalent to alcohol quantity ≥80g/d. alcohol volume (g) conversion formula=alcohol consumption (mL)*alcohol content (%)*0.
- •Abortion less than 30 days prior to screening, pregnant and lactating women (currently breast-feeding or less than one year after delivery although not breast-feeding), women of childbearing potential who are not guaranteed effective contraception during the study, planning pregnancy or donating eggs or sperm within 6 months after the last dose.
- •History of drug abuse or drug addicts.
- •Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.
研究组 & 干预措施
HYML-122 plus cytarabine
The first three eligible enrolled patients will be treated with initial dosing of HYML-122 400mg bid daily and cytarabine 100mg/m2 intravenously by using "3+3" escalating design to explore RP2D. the Data Monitoring Committee (DMC) will evaluate the safety, efficacy and PK data of the phase 1 subjects and establish the combined regimen recommended dose. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgement of the investigator, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet 1 of the discontinuation criteria, whichever occurs first.
干预措施: HYML-122; cytarabine (Drug)
结局指标
主要结局
composite complete remission (CRc) rate
时间窗: up to 24 months.
CRc rate is defined as the rate of all complete and incomplete remission (CRMRD-+CR+CRp+CRi).
ORR
时间窗: up to 24 months
overall remission rate, including complete remission without minimum residual disease (CRMRD-), complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission without platelet recovery (CRp), partial remission (PR).
次要结局
- OS(up to 24 months)
- Incidence of treatment-emergent adverse events (TEAEs)(up to 24 months)
- Cmax,ss(at the end of Cycle 1 (each cycle is 28 days))
- AUCss(at the end of Cycle 1 (each cycle is 28 days))
- RFS(up to 24 months)
- EFS(up to 24 months)
- DOR-CR(up to 24 months)
- Cmin,ss(at the end of Cycle 1 (each cycle is 28 days))
- Cav,ss(at the end of Cycle 1 (each cycle is 28 days))