ECG, Pharmacokinetics, Safety
Conditions
Keywords
gemtuzumab ozogamicin, Mylotarg, QT interval prolongation, Pharmacokinetics, Safety, Veno-occlusive disease, Anti-drug antibody
Brief summary
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.
Detailed description
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.
Interventions
DRUGGemtuzumab Ozogamicin
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 criteria
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
open-label
Intervention model description
Single arm, open-label, interventional
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Refractory or relapsed (ie, bone marrow blasts \>5%) CD33-positive AML. * Age \>=12 years. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2. * Initial peripheral white blood cells (WBC) counts \>=30,000/mL; patients with a higher WBC count should undergo cytoreduction. * Adequate renal/hepatic functions
Exclusion criteria
* Patients with prior treatment with gemtuzumab ozogamicin (GO). * Patients with prior history of VOD/SOS. * Prior HSCT is not allowed, if it was conducted within 2 months prior to study enrollment. * Patients with known active central nervous system (CNS) leukemia. * Uncontrolled or active infectious status. * Uncontrolled cardiac dysrhythmias of NCI CTCAE Grade 2, uncontrolled atrial fibrillation of any grade. * Sero-positivity to human immunodeficieny virus (HIV). * Active hepatitis B or hepatitis C infection * Chemotherapy, radiotherapy, or other anti-cancer therapy (except hydroxyurea as cytoreduction) within 2 weeks prior to enrollment in the study. * Major surgery within 4 weeks prior to enrollment. * QTc interval \>470 milliseconds (msec) using the Fridericia (QTcF), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP). * The use of medications known to predispose to Torsades de Pointes within 2 weeks prior to enrollment * History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemtuzumab ozogamicin (GO).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Positive Anti-Drug Antibody (ADA) | From first dose of study drug up to maximum of 12 months | Percentage of participants 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 outcome measure. |
| Percentage of Participants With Positive Neutralizing Antibodies (NAb) | From first dose of study drug up to maximum of 12 months | Percentage of participants with either treatment-induced NAb or treatment-boosted NAb were reported. |
| Clearance (CL) of Gemtuzumab Ozogamicin | Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7 | Clearance of a drug was measure of the rate at which the drug was metabolized or eliminated by normal biological processes. |
| 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) | 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. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. |
| 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) | Percentage of participants 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. |
| Volume of Distribution of Gemtuzumab Ozogamicin | Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7 | 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. |
| 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 | 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 outcome measure. |
| 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 | Cmax was defined as the maximum observed plasma concentration of GO. Total HP67.6 antibodies analyte was used to determined the Cmax in this outcome measure. |
| 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 | Tmax = time (hours) to maximum plasma concentration (Cmax). |
| 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 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 outcome measure. |
| 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 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 outcome measure. |
| 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 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 outcome measure. |
| 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 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 outcome measure. |
| 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 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 outcome measure. |
| 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 | 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 outcome measure. |
| 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) | An AE was any untoward medical occurrence in a participant 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 hospitalization; 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. |
| 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) | 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 participants 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. |
| 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) | 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 participants 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. |
Countries
Canada, Hungary, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total 66 participants signed the informed consent form and were screened. Out of 66 participants, 15 participants were screen failed and 51 participants were enrolled into the study
Participants by arm
| Arm | Count |
|---|---|
| Gemtuzumab Ozogamicin (GO) Participants 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. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 45 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Gemtuzumab Ozogamicin (GO) |
|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 45 / 50 |
| other Total, other adverse events | 36 / 50 |
| serious Total, serious adverse events | 34 / 50 |
Outcome results
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 1: 1 Hour
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour | 4.90 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 1: 2 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours | 4.25 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 1: 4 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours | 5.10 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 4: 0 Hour
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour | -2.44 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 4: 2 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours | -0.45 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 7: 0 Hour
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour | -1.00 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 7: 2 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours | 4.29 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 7: 4 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours | 4.19 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 1 Day 7: 6 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours | 1.03 milliseconds |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 2 Day 1: 0 Hour
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour | 4.0 milliseconds | Standard Deviation 11.32 |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 2 Day 1: 2 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours | 7.3 milliseconds | Standard Deviation 9.12 |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 2 Day 7: 0 Hour
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour | -5.4 milliseconds | Standard Deviation 7.58 |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 2 Day 7: 2 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours | -1.6 milliseconds | Standard Deviation 10.69 |
Primary
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at 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.
Time frame: Baseline, Cycle 2 Day 7: 6 Hours
Population: QTc analysis set included all the participants in the safety analysis set who had a baseline ECG and at least 1 post-dose ECG. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours | -8.8 milliseconds | Standard Deviation 14.43 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538
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 outcome measure.
Time frame: 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
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 | Cycle 1 Day 1: AC-CL-184538 | 93260 picogram*hour/milliliter | Geometric Coefficient of Variation 83 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 | Cycle 1 Day 1: CL-184538 | 99.83 picogram*hour/milliliter | Geometric Coefficient of Variation 171 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 | Cycle 1 Day 7: AC-CL-184538 | 453900 picogram*hour/milliliter | Geometric Coefficient of Variation 120 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 | Cycle 1 Day 7: CL-184538 | 242.0 picogram*hour/milliliter | Geometric Coefficient of Variation 283 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody
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 outcome measure.
Time frame: 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
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody | Cycle 1 Day 1: Total HP67.6 Antibody | 2496 nanogram*hour/milliliter | Geometric Coefficient of Variation 210 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody | Cycle 1 Day 7: Total HP67.6 Antibody | 14740 nanogram*hour/milliliter | Geometric Coefficient of Variation 388 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538
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 outcome measure.
Time frame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538 | AC-CL-184538 | 461500 picogram*hour/milliliter | Geometric Coefficient of Variation 121 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538 | CL-184538 | 1639 picogram*hour/milliliter | Geometric Coefficient of Variation 181 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody
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 outcome measure.
Time frame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody | 26820 nanogram*hour/milliliter | Geometric Coefficient of Variation 131 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538
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 outcome measure.
Time frame: Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538 | AC-CL-184538 | 93490 picogram*hour/milliliter | Geometric Coefficient of Variation 82 |
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538 | CL-184538 | 247.8 picogram*hour/milliliter | Geometric Coefficient of Variation 176 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody
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 outcome measure.
Time frame: Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody | 3797 nanogram*hour/milliliter | Geometric Coefficient of Variation 135 |
Secondary
Clearance (CL) of Gemtuzumab Ozogamicin
Clearance of a drug was measure of the rate at which the drug was metabolized or eliminated by normal biological processes.
Time frame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Population: Pharmacokinetic (PK) analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Clearance (CL) of Gemtuzumab Ozogamicin | AC-CL-184538 | 15.02 Liters/hour | Geometric Coefficient of Variation 112 |
| Gemtuzumab Ozogamicin (GO) | Clearance (CL) of Gemtuzumab Ozogamicin | CL-184538 | 4246 Liters/hour | Geometric Coefficient of Variation 177 |
| Gemtuzumab Ozogamicin (GO) | Clearance (CL) of Gemtuzumab Ozogamicin | Total HP67.6 Antibody | 0.3212 Liters/hour | Geometric Coefficient of Variation 153 |
Secondary
Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538
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 outcome measure.
Time frame: 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
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 | Cycle 1 Day 1: AC-CL-184538 | 6457 picogram/milliliter | Geometric Coefficient of Variation 81 |
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 | Cycle 1 Day 1: CL-184538 | 45.69 picogram/milliliter | Geometric Coefficient of Variation 51 |
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 | Cycle 1 Day 7: AC-CL-184538 | 11740 picogram/milliliter | Geometric Coefficient of Variation 79 |
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 | Cycle 1 Day 7: CL-184538 | 58.76 picogram/milliliter | Geometric Coefficient of Variation 70 |
Secondary
Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody
Cmax was defined as the maximum observed plasma concentration of GO. Total HP67.6 antibodies analyte was used to determined the Cmax in this outcome measure.
Time frame: 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
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody | Cycle 1 Day 1: Total HP67.6 Antibody | 282.1 nanogram/milliliter | Geometric Coefficient of Variation 77 |
| Gemtuzumab Ozogamicin (GO) | Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody | Cycle 1 Day 7: Total HP67.6 Antibody | 585.6 nanogram/milliliter | Geometric Coefficient of Variation 105 |
Secondary
Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters
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 participants 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.
Time frame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters | 18 Participants |
Secondary
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
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 participants 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.
Time frame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | 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 | 43 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant 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 hospitalization; 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.
Time frame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | TEAEs | 49 Participants |
| Gemtuzumab Ozogamicin (GO) | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 34 Participants |
Secondary
Overall Survival (OS)
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. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Time frame: From the first dose of study treatment to the date of death or date of censored, whichever occurred first (maximum up to 12 months)
Population: Full analysis set included all enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Overall Survival (OS) | 2.8 months |
Secondary
Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)
Percentage of participants 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.
Time frame: From first dose of study drug to 36 days after last dose (maximum up to of 12 months)
Population: Full analysis set included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi) | 9.8 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Percentage of participants 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 outcome measure.
Time frame: From first dose of study drug up to maximum of 12 months
Population: Immunogenicity analysis set included all participants in the safety analysis set who had at least 1 immunogenicity sample with results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Percentage of Participants With Positive Anti-Drug Antibody (ADA) | Treatment-induced ADA Positive | 12.0 percentage of participants |
| Gemtuzumab Ozogamicin (GO) | Percentage of Participants With Positive Anti-Drug Antibody (ADA) | Treatment-boosted ADA Positive | 0.0 percentage of participants |
Secondary
Percentage of Participants With Positive Neutralizing Antibodies (NAb)
Percentage of participants with either treatment-induced NAb or treatment-boosted NAb were reported.
Time frame: From first dose of study drug up to maximum of 12 months
Population: Immunogenicity analysis set included all participants in the safety analysis set who had at least 1 immunogenicity sample with results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Percentage of Participants With Positive Neutralizing Antibodies (NAb) | 2.0 percentage of participants |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax = time (hours) to maximum plasma concentration (Cmax).
Time frame: 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
Population: PK analysis set included all the participants who were treated with GO and contributed at least 1 PK sample. Here, 'Number Analyzed' = participants evaluable for this outcome measure for specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 1: AC-CL-184538 | 2.080 hours |
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 1: CL-184538 | 2.170 hours |
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 1: Total HP67.6 Antibody | 2.080 hours |
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 7: AC-CL-184538 | 2.130 hours |
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 7: CL-184538 | 3.920 hours |
| Gemtuzumab Ozogamicin (GO) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 Day 7: Total HP67.6 Antibody | 2.170 hours |
Secondary
Volume of Distribution of Gemtuzumab Ozogamicin
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.
Time frame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Population: This outcome measure could not be estimated due to insufficient concentration-time data by non-compartmental analysis.