A SINGLE ARM, OPEN-LABEL, PHASE 4 STUDY EVALUATING QT INTERVAL, PHARMACOKINETICS, AND SAFETY OF GEMTUZUMAB OZOGAMICIN (MYLOTARG (TRADEMARKER)) AS A SINGLE-AGENT REGIMEN IN PATIENTS WITH RELAPSED OR REFRACTORY CD33-POSITIVE ACUTE MYELOID LEUKEMIA
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 51
- 试验地点
- 24
- 主要终点
- Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour
研究概览
简要总结
This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc, pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and pediatric patients with relapsed or refractory CD33-positive AML.
详细描述
This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc, pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and pediatric patients with relapsed or refractory CD33-positive AML. Approximately 50 adult (age >=18 years) and 6 pediatric (12 years =< age =< 17 years) patients who satisfy the study eligibility criteria will be enrolled. Enrolled patients will receive GO 3 mg/m2 up to 2 cycles on Days 1, 4, and 7 at each cycle. The impact of GO on VOD/SOS in the context of previous and subsequent HSCT will also be assessed. Patients enrolled in the study will receive three doses of GO 3 mg/m2 (up to one vial) as a 2-hour intravenous infusion on Cycle 1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7 will be allowed at the investigator's discretion for patients who meet the following criteria after Cycle 1: Bone marrow with a decrease of blast percentage to at least 25% or a decrease of pretreatment blast percentage by at least 50%; and Blood count with neutrophils >=1,000/µL, and platelets >=50,000/µL, except in patients with the bone marrow blasts >=5%, the decrease in neutrophils and platelets thought to be due to the underlying leukemia. After GO treatment, subsequent anticancer therapy such as consolidation or conditioning regimen and/or HSCT could be considered at the investigator's discretion. A minimum interval of 2 months is recommended between the last dose of GO and HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open-label
入排标准
- 年龄范围
- 12 Years 至 —（Child, 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
Gemtuzumab Ozogamicin (GO)
Patients will receive three doses of Gemtuzumab Ozogamicin (GO) 3 mg/m2 (up to one vial) as a 2 hour intravenous infusion on Cycle 1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7 will be allowed at the investigator's discretion for patients who meet the criteria
干预措施: Gemtuzumab Ozogamicin (Drug)
结局指标
主要结局
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour
时间窗: Baseline, Cycle 1 Day 1: 1 Hour
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours
时间窗: Baseline, Cycle 1 Day 1: 2 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours
时间窗: Baseline, Cycle 1 Day 1: 4 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour
时间窗: Baseline, Cycle 1 Day 4: 0 Hour
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours
时间窗: Baseline, Cycle 1 Day 4: 2 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour
时间窗: Baseline, Cycle 1 Day 7: 0 Hour
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours
时间窗: Baseline, Cycle 1 Day 7: 2 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours
时间窗: Baseline, Cycle 1 Day 7: 4 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours
时间窗: Baseline, Cycle 1 Day 7: 6 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour
时间窗: Baseline, Cycle 2 Day 1: 0 Hour
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours
时间窗: Baseline, Cycle 2 Day 1: 2 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour
时间窗: Baseline, Cycle 2 Day 7: 0 Hour
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours
时间窗: Baseline, Cycle 2 Day 7: 2 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours
时间窗: Baseline, Cycle 2 Day 7: 6 Hours
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.
次要结局
- Clearance (CL) of Gemtuzumab Ozogamicin(Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Volume of Distribution of Gemtuzumab Ozogamicin(Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1)
- Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody(Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1)
- Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538(Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody(Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7)
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months))
- Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Hematology and Coagulation Parameters(From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months))
- Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters(From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months))
- Percentage of Participants With Positive Anti-Drug Antibody (ADA)(From first dose of study drug up to maximum of 12 months)
- Overall Survival (OS)(From the first dose of study treatment to the date of death or date of censored, whichever occurred first (maximum up to 12 months))
- Percentage of Participants With Positive Neutralizing Antibodies (NAb)(From first dose of study drug up to maximum of 12 months)
- Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)(From first dose of study drug to 36 days after last dose (maximum up to of 12 months))