A Phase 1 Study to Assess the Safety and Antitumor Activity of APL-4098 Alone and in Combination With Azacitidine and in Combination With Azacitidine Plus Venetoclax in Adults With Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome/AML (MDS/AML) or Myelodysplastic Syndrome With Excess Blasts (MDS-EB)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 14
- 主要终点
- Incidence of Treatment Emergent Adverse Events [Safety]
研究概览
简要总结
This is an open-label, Phase 1 study to determine the safety, tolerability, and efficacy of APL-4098 alone, and in combination with azacitidine, and in combination with azacitidine plus venetoclax for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •18 years or older
- •Confirmed diagnosis of relapsed refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS)/ AML, or MDS-excess blasts (MDS-EB) with the following characteristics: - R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit.
- •WBC count ≤ 25,000/microliter
- •ECOG Performance Status of ≤ 2
- •Weight ≥ 40kg
- •Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse
- •Male participants must be willing to use specific contraception and not plan to impregnant a female partner or donate sperm while on study
- •Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial
排除标准
- •Certain prior therapies such as: received an allogeneic stem cell transplant within 6 months of screening, received an autologous stem cell transplant within 3 months of screening, received any anti-cancer treatments within 2 weeks of Cycle 1 Day 1, prior radiation therapy within 4 weeks of screening
- •Certain medical conditions such as: other malignancies, myocardial infarction within 6 months of screening, symptomatic congestive heart failure, uncontrolled active infection, history of arterial thrombosis within 6 months of screening
- •Diagnostic assessments: Left ventricular ejection fraction < 45%, Fridericia's corrected QT interval > 470msec, Aspartate aminotransferase and/or alanine aminotransferase > 3 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN, calculated or measured creatinine clearance < 45 mL/minute (multiply by 0.85 if female)
- •Infectious disease: HIV positive, active hepatitis B and/or C
研究组 & 干预措施
APL-4098 and azacitidine and venetoclax
Dose escalation with different dosing levels of APL-4098 in combination with azacitidine and venetoclax.
干预措施: Azacitidine and Venetoclax and APL-4098 (Drug)
Dose Escalation Phase: APL-4098 monotherapy
Dose escalation with different dosing levels of APL-4098.
干预措施: APL-4098 (Drug)
Dose Escalation Phase: APL-4098 and azacitidine
Dose escalation with different dosing levels of APL-4098 in combination with azacitidine.
干预措施: Azacitidine and APL-4098 (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events [Safety]
时间窗: Through study completion, approximately one year
Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, Electrocardiogram results
Incidence of Dose Limiting Toxicities [Tolerability]
时间窗: Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, and Electrocardiogram results
Determine Recommended Phase 2 Dose (RP2D)/Recommended dose range (RDR) levels of APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax.
时间窗: Approximately one year
Assess the Pharmacokinetics of APL-4098
时间窗: On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Evaluate PK parameters: Maximum plasma concentration (Cmax)
次要结局
- Assess response to disease with APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax.(Response is assessed at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 (each cycle is 28 days long), then every three cycles thereafter (assessed for up to 2 years))