A Phase I, Open-label, Cohort Dose Escalation Trial With BI 836858 in Patients With Refractory or Relapsed Acute Myeloid Leukemia and Patients With Acute Myeloid Leukemia in Complete Remission With High Risk to Relapse.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Determination of the Maximum Tolerated Dose (MTD) of BI 836858
研究概览
简要总结
Patients with acute myeloid leukemia who experience a relapse after at least one prior regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are in complete remission with high risk to relapse may be eligible for this trial. The trial will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose levels.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BI836858 10milligram(mg)(Patients with relapsed\refractoryAML)
Patients with relapsed\refractory AML were administered BI 836858 10 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations).
干预措施: BI 836858 (Drug)
BI 836858 20 mg (Patients with relapsed\refractory AML)
Patients with relapsed\refractory AML were administered BI 836858 20 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations).
干预措施: BI 836858 (Drug)
BI 836858 40 mg (Patients with relapsed\refractory AML)
Patients with relapsed\refractory AML were administered BI 836858 40 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations).
干预措施: BI 836858 (Drug)
BI 836858 40 mg (Patients with AML in CR)
Patients with AML in complete remission (CR) with high risk to relapse were administered BI 836858 40 mg solution for infusion intravenously on Day 1 of Cycles 1, 2 and 3. From the 4th administration onwards, patients received monthly (every second cycle) infusions (i.e. 4th infusion on Cycle 5 Day 1, 5th infusion on Cycle 7 Day 1, etc.) for overall up to 12 months of treatment unless the patient relapsed or infusions were not tolerated.
干预措施: BI 836858 (Drug)
结局指标
主要结局
Determination of the Maximum Tolerated Dose (MTD) of BI 836858
时间窗: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.
This trial was discontinued prior to reaching the primary endpoint of determining MTD.
Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation
时间窗: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.
Dose limiting toxicity was defined as any non-disease-related, non-hematological Adverse Events (AE) of Common Terminology Criteria for AE (CTCAE) grade 3 or higher. Number of patients with DLT during the MTD evaluation period for evaluation for patients with refractory or relapsed acute myeloid leukemia, the first 2 cycles (i.e. patient received at least 4 administrations of BI 836858 and reached end of Cycle 2) and for AML patients in CR with high risk to relapse, the first 2 cycles (i.e. patient has received at least 2 administrations of BI 836858 and reached end of Cycle 2).
次要结局
- Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD)(From first administration of study drug until the earliest of progressive disease (PD), death or last adequate disease assessment before new anti-cancer therapy, up to 299 days.)
- Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia(From first administration of study drug until progressive disease, relapse, death or start of next anti-AML therapy, up to 167 days.)
- Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia(From first administration of study drug until progressed according to disease assessment, relapse, or death without progression, up to 167 days.)
- Progression Free Survival for AML Patients in CR With High Risk to Relapse(From first treatment with study drug until disease progression, relapse or death for AML patients in CR with high risk to relapse, up to 409 days.)
- Time to Treatment Failure for AML Patients in CR With High Risk to Relapse(From first treatment with study drug until disease progression, relapse, death or start of next AML therapy for AML patients in CR with high risk to relapse, up to 409 days.)
- Maximum Measured Plasma Concentration (Cmax)(At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion.)
- Time From Dosing to the Maximum Plasma Concentration (Tmax)(At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion.)
- Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168)(At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after BI 836858 infusion.)
- Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz)(At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion.)
- Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Terminal Half-life (t1/2)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Mean Residence Time After Intravenous Infusion (MRT)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Total Plasma Clearance (CL)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Apparent Volume of Distribution During the Terminal Phase (Vz)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Volume of Distribution After Intravenous Infusion at Steady State (Vss)(At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.)
- Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz)(At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion.)