A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 30
- 试验地点
- 7
- 主要终点
- Maximum observed plasma concentration (Cmax) of ABBV-744
研究概览
简要总结
This is an open-label, Phase 1, dose-escalation (Segment 1) and expansion (Segment 2) study to determine the maximum tolerated dose (MTD) and/or the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-744 in participants with relapsed/refractory Acute Myeloid Leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participant must have AML not amenable to curative therapy, refractory to standard of care therapy or for which standard of care therapy does not exist. Participants who are candidates for stem cell transplantation must have been offered this therapeutic option.
- •Must consent to provide biomarker analyses as described in the protocol.
- •Must have an Eastern Cooperative Oncology Group (ECOG) Performance status of:
- •Dose Escalation (Segment 1): 0 - 1
- •Dose Expansion (Segment 2): 0 - 2
- •Dose Escalation: Must have a serum albumin during Screening of >= 3.0 g/dL.
- •Participant has adequate bone marrow, renal and hepatic function.
排除标准
- •Participant with known active Central Nervous System (CNS) disease.
- •Participant has received anti-cancer traditional medicine or anti-cancer herbal remedies within 14 days prior to ABBV-744 dosing. Saw palmetto is considered anti-cancer herbal remedy. Participant has received anti-cancer therapy within a period of 14 days or 5 half-lives (whichever is longer; except for immunotherapy where a period of 21 days will be acceptable) prior to Study Day
- •Except for hydroxyurea which will be allowed during screening and treatment for controlling leukocytosis.
- •Participant has been previously treated with a Bromodomain and Extra-Terminal (BET) inhibitor
- •Participant has unresolved clinically significant toxicities from most recent prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE v 4.03) grade 2 or higher clinically significant toxicity (excluding alopecia).
- •Participant has received the following within 7 days prior to the first dose of study drug: corticosteroid therapy, CYP3A inhibitors, CYP3A inducers.
- •Participant consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
- •Participant had major surgery within 28 days prior to Study Day
- •Participant is unable to swallow or absorb oral tablets.
- •Participant has known infection with hepatitis B or hepatitis C.
- •Participant has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis, enteritis, colitis.
- •Participant has symptoms of gross hematuria or gross hemoptysis
- •Has electrocardiogram with a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 msec or ECG with second degree type 2 or third degree atrioventricular block.
研究组 & 干预措施
ABBV-744 Dose Escalation
ABBV-744 will be administered at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.
干预措施: ABBV-744 (Drug)
ABBV-744 Dose Expansion
ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.
干预措施: ABBV-744 (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax) of ABBV-744
时间窗: Through Cycle 2 ( each cycle is 28 days)
Cmax of ABBV-744.
Time to Cmax (Tmax) of ABBV-744
时间窗: Through Cycle 2 ( each cycle is 28 days)
Tmax of ABBV-744.
Maximum Tolerated Dose (MTD) for ABBV-744
时间窗: Up to 28 days after first dose of study drug
The MTD is defined as the highest dose for which the estimated posterior mean DLT rate is \<= 33% and excessive toxicity probability is limited to maximum of 25% during the first 28 days.
Recommended Phase 2 Dose (RPTD) for ABBV-744
时间窗: Up to 28 days after first dose of study drug
RPTD will be determined from a review available safety, pharmacokinetic, and efficacy data during the dose escalation phase (Segment 1) of the study.
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744
时间窗: Through Cycle 2 ( each cycle is 28 days)
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744.
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744
时间窗: Through Cycle 2 ( each cycle is 28 days)
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744.
Terminal Phase Elimination Rate Constant (β) of ABBV-744
时间窗: Through Cycle 2 ( each cycle is 28 days)
Terminal Phase Elimination Rate Constant (β) of ABBV-744.
Dose-limiting toxicity (DLT) of ABBV-744
时间窗: Up to 28 days after first dose of study drug
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.
次要结局
- Composite complete remission (CRc)(Up to 2 years)
- Complete Remission (CR) + CR with partial hematologic recovery (CRh)(Up to 2 years)
- Objective Response Rate (ORR)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Event-free survival (EFS)(Up to 2 years)