Clinical Trial Results:
A Single arm, Open-Label, Phase 4 Study Evaluating QT Interval, Pharmacokinetics, and Safety of Gemtuzumab Ozogamicin (Mylotarg) as a Single-Agent Regimen in Subjects With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia.
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Summary
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EudraCT number |
2018-002619-89 |
Trial protocol |
DE GB HU PL ES |
Global end of trial date |
27 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Nov 2021
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First version publication date |
10 Nov 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B1761031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03727750 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Aug 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assessed the effect of GO on the QTc interval.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 5
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Country: Number of subjects enrolled |
Hungary: 7
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Country: Number of subjects enrolled |
Poland: 12
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Country: Number of subjects enrolled |
Spain: 14
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
51
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EEA total number of subjects |
33
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
32
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in 6 countries from 03 July 2019 to 27 April 2021. A total of 51 subjects were enrolled. | ||||||||||||||||
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Pre-assignment
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Screening details |
Total 66 subjects signed the informed consent form and were screened. From the 66 subjects, 51 subjects were enrolled in the study. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Gemtuzumab Ozogamicin (GO) | ||||||||||||||||
Arm description |
Subjects with confirmed diagnosis of refractory or relapsed cluster of differentiation (CD33)- positive Acute Myeloid Leukemia (AML) aged greater than or equal to (>=) 18 years received three doses of Gemtuzumab Ozogamicin, 3 milligram per meter square (mg/m^2) as intravenous (IV) infusion on Days 1, 4 and 7 of Cycle 1 and 2. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Gemtuzumab Ozogamicin
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Investigational medicinal product code |
CMA-676
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received three doses of gemtuzumab ozogamicin as IV infusion on Days 1, 4 and 7 of Cycle 1 and 2.
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Baseline characteristics reporting groups
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Reporting group title |
Gemtuzumab Ozogamicin (GO)
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Reporting group description |
Subjects with confirmed diagnosis of refractory or relapsed cluster of differentiation (CD33)- positive Acute Myeloid Leukemia (AML) aged greater than or equal to (>=) 18 years received three doses of Gemtuzumab Ozogamicin, 3 milligram per meter square (mg/m^2) as intravenous (IV) infusion on Days 1, 4 and 7 of Cycle 1 and 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Gemtuzumab Ozogamicin (GO)
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Reporting group description |
Subjects with confirmed diagnosis of refractory or relapsed cluster of differentiation (CD33)- positive Acute Myeloid Leukemia (AML) aged greater than or equal to (>=) 18 years received three doses of Gemtuzumab Ozogamicin, 3 milligram per meter square (mg/m^2) as intravenous (IV) infusion on Days 1, 4 and 7 of Cycle 1 and 2. | ||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 1: 1 Hour [1] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 1: 1 Hour
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 1: 2 Hours [2] | ||||||||
End point description |
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. Corrected QT interval using Fridericia's heart rate correction 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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 1: 2 Hours
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 1: 4 Hours [3] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 1: 4 Hours
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 4: 2 Hours [4] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 4: 2 Hour
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 4: 0 Hour [5] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 4: 0 Hour
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 7: 2 Hours [6] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 7: 2 Hours
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 7: 0 Hour [7] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 7: 0 Hour
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 7: 4 Hours [8] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 7: 4 Hours
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 1 Day 7: 6 Hours [9] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 1 Day 7: 6 Hours
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 2 Day 1: 2 Hours [10] | ||||||||
End point description |
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. Corrected QT interval using Fridericia's heart rate correction 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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 2 Day 1: 2 Hours
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 2 Day 1: 0 Hour [11] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 2 Day 1: 0 Hour
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 2 Day 7: 0 Hour [12] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 2 Day 7: 0 Hour
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 2 Day 7: 2 Hours [13] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 2 Day 7: 2 Hours
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia’s Formula (QTcF) at Cycle 2 Day 7: 6 Hours [14] | ||||||||
End point description |
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. QTc analysis set included all the subjects in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Cycle 2 Day 7: 6 Hours
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| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Clearance (CL) of Gemtuzumab Ozogamicin | ||||||||||||||
End point description |
Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Pharmacokinetic (PK) analysis set included all subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint for specified rows.
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End point type |
Secondary
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End point timeframe |
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 | ||||||||||||||||
End point description |
Cmax was defined as the maximum observed plasma concentration of GO. Calicheamicin (conjugated calicheamicin ac-CL-184538 and unconjugated CL-184538) analyte were used to determined the Cmax in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint at specific time point.
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End point type |
Secondary
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End point timeframe |
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
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Volume of Distribution of Gemtuzumab Ozogamicin | ||||||||
End point description |
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
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End point type |
Secondary
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End point timeframe |
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
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| Notes [15] - Endpoint not estimated due to insufficient concentration-time data by non-compartmental analysis. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody | ||||||||||||
End point description |
Cmax was defined as the maximum observed plasma concentration of GO. Total HP67.6 antibodies analyte was used to determined the Cmax in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint at specific time point.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||
End point title |
Time to Reach Maximum Observed Plasma Concentration (Tmax) | ||||||||||||||||||||
End point description |
Tmax = time (hours) to reach maximum plasma concentration (Cmax). PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint at specific time point.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 | ||||||||||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast). Calicheamicin (conjugated calicheamicin ac-CL-184538 and unconjugated CL-184538) analytes were used to determined the AUClast in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint at specific time point.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
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
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody | ||||||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast). Total HP67.6 antibodies analyte was used to determined the AUClast in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint at specific time point.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538 | ||||||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time 72 hours (AUC0-72). Calicheamicin (conjugated calicheamicin ac-CL-184538 and unconjugated CL-184538) analytes were used to determined the AUC0-72 in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint for specified rows.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody | ||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time 72 hours (AUC0-72). Total HP67.6 antibodies analyte was used to determined the AUC0-72 in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538 | ||||||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time 336 hours (AUC0-336). Calicheamicin (conjugated calicheamicin ac-CL-184538 and unconjugated CL-184538) analytes were used to determined the AUC0-336 in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘n’ = subjects evaluable for this endpoint for specified rows.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody | ||||||||
End point description |
Area under the plasma concentration-time curve from time zero to the time 336 hours (AUC0-336). Total HP67.6 antibodies analyte was used to determined the AUC0-336 in this endpoint. PK analysis set included all the subjects who were treated with GO and contributed at least 1 PK sample. Here, ‘Number of Subject Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | ||||||||||
End point description |
An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalisation; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event between first dose of study drug and up to 36 days after the last dose of study drug, that was absent before treatment, or that worsened during the treatment period relative to the pretreatment state. AEs included all serious and non-serious adverse events. Safety analysis set included all enrolled subjects who received at least 1 dose of study medication.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||
End point title |
Number of Subjects With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Hematology and Coagulation Parameters | ||||||
End point description |
Laboratory parameters included hematological and coagulation parameters. These included activated partial thromboplastin time prolonged, anemia, fibrinogen decreased, hemoglobin increased, international normalized ratio increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased. Number of subjects with hematological and coagulation abnormalities by grades (as per Common Terminology Criteria for Adverse Events (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Safety analysis set included all enrolled subjects who received at least 1 dose of study medication.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||
End point title |
Percentage of Subjects With Positive Anti-Drug Antibody (ADA) | ||||||||||||
End point description |
Percentage of subjects with treatment-induced ADA positive (post baseline-positive only) and treatment-boosted ADA positive (baseline ADA titer that was boosted to a 9-fold or higher level following drug administration) were reported in this endpoint. Immunogenicity analysis set included all subjects in the safety analysis set who had at least 1 immunogenicity sample with results.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose of study drug up to maximum of 12 months
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||
End point title |
Number of Subjects With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters | ||||||
End point description |
Laboratory parameters included chemistry parameters. These included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia. Number of subjects with chemistry test abnormalities by grades (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Safety analysis set included all enrolled subjects who received at least 1 dose of study medication.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Percentage of Subjects With Positive Neutralizing Antibodies (NAb) | ||||||||
End point description |
Percentage of subjects who had post baseline positive ADA response were evaluated for NAb. Immunogenicity analysis set included all subjects in the safety analysis set who had at least 1 immunogenicity sample with results.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to maximum of 12 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Percentage of Subjects who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi) | ||||||||||
End point description |
Percentage of subjects with first dose of study drug to best overall response with CR and CRi were reported. CR was defined as the disappearance of leukemia indicated by less than (<) 5 percent (%) bone marrow blasts, absence of circulating blasts with Auer rods and absence of extramedullary disease, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (>=)1000 per microliter (1000/mcL) and platelets >=100,000/mcL. CRi was defined as all CR criteria except residual neutropenia; ANC <1000/mcL or thrombocytopenia and platelet count <100,000/mcL. Full analysis set included all enrolled subjects.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
From first dose of study drug to 36 days after last dose (maximum up to of 12 months)
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||
End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time (in months) from the start date (first dose) of study treatment to the date of death due to any cause. Subjects last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. Full analysis set included all enrolled subjects
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study treatment to the date of death or date of censored, whichever occurred first (maximum up to 12 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
|
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Adverse event reporting additional description |
Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety analysis set analysed.
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
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|
Reporting groups
|
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Reporting group title |
Gemtuzumab Ozogamicin (GO)
|
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Reporting group description |
Subjects with confirmed diagnosis of refractory or relapsed CD33-positive Acute Myeloid Leukemia (AML) aged >= 18 years received three doses of Gemtuzumab Ozogamicin, 3 mg/m^2 as IV infusion on Days 1, 4 and 7 of Cycle 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
