A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study of BMF-500, an Oral Covalent FLT3 Inhibitor, in Adults With Acute Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 14
- 主要终点
- Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs).
研究概览
简要总结
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral FLT3 inhibitor, in adult patients with acute leukemia.
详细描述
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adult patients with acute myeloid leukemia (AML), who may or may not be on Antifungals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years.
- •Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
- •ECOG performance status of 0-
- •Adequate liver and renal function
- •Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
- •Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
- •Arm B: Participants must have received a necessary azole antifungal(s) that is a strong CYP3A4 inhibitor (excluding other strong CYP3A4 inhibitor[s]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.
- •Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks (Cycle 1).
排除标准
- •Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within 6 months prior to the first dose of the trial intervention.
- •WBC count >50,000/µL (uncontrollable with cytoreductive therapy).
- •Women who are pregnant or lactating or plan to become pregnant.
研究组 & 干预措施
Arm A: Escalation Phase
BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity.
干预措施: BMF-500 (Drug)
Arm B: Escalation Phase
BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are Strong CYP3A4 inhibitors.
干预措施: BMF-500 (Drug)
Arm C: Escalation Phase
BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are moderate CYP3A4 inhibitors.
干预措施: BMF-500 (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs).
时间窗: At the end of each 28 Day cycle for a maximum of 32 cycles
Assessed by the NCI CTCAE version 5.0.
Evaluate the safety and tolerability of BMF-500 by incidence of Serious Adverse Events (SAEs).
时间窗: At the end of each 28 Day cycle for a maximum of 32 cycles
Assessed by the NCI CTCAE version 5.0.
Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
时间窗: At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0.
次要结局
- Determine the pharmacokinetics of BMF-500.(At the end of Cycle 1 and 2 (each cycle is 28 days in duration))
- Evaluate the efficacy of BMF-500(At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles)
- Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.(At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles)
- Determine the pharmacokinetics of BMF-500.(At the end of each cycle (each cycle is 28 days in duration) for 7 cycles)