Evaluating QTc, PK, Safety of Gemtuzumab Ozogamicin (GO) in Patients With CD33+ R/R AML

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03727750
Collaborator
(none)
51
24
1
21.8
2.1
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Gemtuzumab Ozogamicin
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
51 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single arm, open-label, interventionalSingle arm, open-label, interventional
Masking:
None (Open Label)
Masking Description:
open-label
Primary Purpose:
Treatment
Official Title:
A SINGLE ARM, OPEN-LABEL, PHASE 4 STUDY EVALUATING QT INTERVAL, PHARMACOKINETICS, AND SAFETY OF GEMTUZUMAB OZOGAMICIN (MYLOTARG (TRADEMARKER)) AS A SINGLE-AGENT REGIMEN IN PATIENTS WITH RELAPSED OR REFRACTORY CD33-POSITIVE ACUTE MYELOID LEUKEMIA
Actual Study Start Date :
Jul 3, 2019
Actual Primary Completion Date :
Apr 27, 2021
Actual Study Completion Date :
Apr 27, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Gemtuzumab Ozogamicin (GO)

Patients will receive three doses of Gemtuzumab Ozogamicin (GO) 3 mg/m2 (up to one vial) as a 2 hour intravenous infusion on Cycle 1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7 will be allowed at the investigator's discretion for patients who meet the criteria

Drug: Gemtuzumab 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

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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 Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody [Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7]

    Area under the plasma concentration-time 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years and Older
Sexes Eligible for Study:
All
Accepts 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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Augusta University Medical Center Clinical Research Pharmacy Augusta Georgia United States 30912
2 Georgia Cancer Center at Augusta University Augusta Georgia United States 30912
3 Brody School of Medicine at East Carolina University Greenville North Carolina United States 27834
4 Vidant Medical Center Greenville North Carolina United States 27834
5 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
6 Research Transition Facility Edmonton Alberta Canada T6G 2V2
7 Kaye Edmonton Clinic Edmonton Alberta Canada T6G1Z1
8 Hamilton Health Sciences, Juravinski Hospital Hamilton Ontario Canada L8V 1C3
9 Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
10 Semmelweis Egyetem I.sz Belgyogyaszati Klinika, Hematologiai Osztaly Budapest Hungary 1083
11 Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika Debrecen Hungary 4032
12 Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat - Hematologiai Osztaly Gyor Hungary 9024
13 Somogy Megyei Kaposi Mor Oktato Korhaz Kaposvar Hungary 7400
14 Klinika Hematologii i Transplantologii Gdansk Poland 80-214
15 Uniwersyteckie Centrum Kliniczne Gdansk Poland 80-214
16 Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku Wroclaw Poland 50-367
17 Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego Wroclaw Poland 50-369
18 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08025
19 Hospital Universitario Reina Sofía Cordoba Spain 14004
20 Hospital General Universitario Gregorio Maranon Madrid Spain 28007
21 Hospital Universitari i Politecnic La Fe Valencia Spain 46026
22 The Royal Bournemouth and Christchurch NHS Foundation Trust Bournemouth Dorset United Kingdom BH7 7DW
23 Belfast Health and Social Care Trust Belfast United Kingdom BT9 7AB
24 Clatterbridge Cancer Center NHS Foundation Trust Liverpool United Kingdom L7 8XP

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03727750
Other Study ID Numbers:
  • B1761031
  • 2018-002619-89
First Posted:
Nov 1, 2018
Last Update Posted:
Mar 25, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 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
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description Participants 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.
Period Title: Overall Study
STARTED 51
Safety Set 50
COMPLETED 2
NOT COMPLETED 49

Baseline Characteristics

Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Overall Participants 51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
64.9
(11.4)
Sex: Female, Male (Count of Participants)
Female
20
39.2%
Male
31
60.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
6
11.8%
Not Hispanic or Latino
40
78.4%
Unknown or Not Reported
5
9.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
3
5.9%
White
39
76.5%
More than one race
0
0%
Unknown or Not Reported
9
17.6%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour
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.
Time Frame Baseline, Cycle 1 Day 1: 1 Hour

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 48
Least Squares Mean (90% Confidence Interval) [milliseconds]
4.90
2. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours
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.
Time Frame Baseline, Cycle 1 Day 1: 2 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 46
Least Squares Mean (90% Confidence Interval) [milliseconds]
4.25
3. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours
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.
Time Frame Baseline, Cycle 1 Day 1: 4 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 49
Least Squares Mean (90% Confidence Interval) [milliseconds]
5.10
4. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour
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.
Time Frame Baseline, Cycle 1 Day 4: 0 Hour

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 47
Least Squares Mean (90% Confidence Interval) [milliseconds]
-2.44
5. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours
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.
Time Frame Baseline, Cycle 1 Day 4: 2 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 46
Least Squares Mean (90% Confidence Interval) [milliseconds]
-0.45
6. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour
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.
Time Frame Baseline, Cycle 1 Day 7: 0 Hour

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 44
Least Squares Mean (90% Confidence Interval) [milliseconds]
-1.00
7. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours
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.
Time Frame Baseline, Cycle 1 Day 7: 2 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 45
Least Squares Mean (90% Confidence Interval) [milliseconds]
4.29
8. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours
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.
Time Frame Baseline, Cycle 1 Day 7: 4 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 44
Least Squares Mean (90% Confidence Interval) [milliseconds]
4.19
9. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours
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.
Time Frame Baseline, Cycle 1 Day 7: 6 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 45
Least Squares Mean (90% Confidence Interval) [milliseconds]
1.03
10. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour
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.
Time Frame Baseline, Cycle 2 Day 1: 0 Hour

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 9
Mean (Standard Deviation) [milliseconds]
4.0
(11.32)
11. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours
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.
Time Frame Baseline, Cycle 2 Day 1: 2 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 9
Mean (Standard Deviation) [milliseconds]
7.3
(9.12)
12. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour
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.
Time Frame Baseline, Cycle 2 Day 7: 0 Hour

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 9
Mean (Standard Deviation) [milliseconds]
-5.4
(7.58)
13. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours
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.
Time Frame Baseline, Cycle 2 Day 7: 2 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 9
Mean (Standard Deviation) [milliseconds]
-1.6
(10.69)
14. Primary Outcome
Title Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours
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.
Time Frame Baseline, Cycle 2 Day 7: 6 Hours

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 9
Mean (Standard Deviation) [milliseconds]
-8.8
(14.43)
15. Secondary Outcome
Title Clearance (CL) of Gemtuzumab Ozogamicin
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
AC-CL-184538
15.02
(112)
CL-184538
4246
(177)
Total HP67.6 Antibody
0.3212
(153)
16. Secondary Outcome
Title Volume of Distribution of Gemtuzumab Ozogamicin
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.
Time Frame Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

Outcome Measure Data

Analysis Population Description
This outcome measure could not be estimated due to insufficient concentration-time data by non-compartmental analysis.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 0
17. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538
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 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Cycle 1 Day 1: AC-CL-184538
6457
(81)
Cycle 1 Day 1: CL-184538
45.69
(51)
Cycle 1 Day 7: AC-CL-184538
11740
(79)
Cycle 1 Day 7: CL-184538
58.76
(70)
18. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody
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 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Cycle 1 Day 1: Total HP67.6 Antibody
282.1
(77)
Cycle 1 Day 7: Total HP67.6 Antibody
585.6
(105)
19. Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Cycle 1 Day 1: AC-CL-184538
2.080
Cycle 1 Day 1: CL-184538
2.170
Cycle 1 Day 1: Total HP67.6 Antibody
2.080
Cycle 1 Day 7: AC-CL-184538
2.130
Cycle 1 Day 7: CL-184538
3.920
Cycle 1 Day 7: Total HP67.6 Antibody
2.170
20. Secondary Outcome
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
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 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Cycle 1 Day 1: AC-CL-184538
93260
(83)
Cycle 1 Day 1: CL-184538
99.83
(171)
Cycle 1 Day 7: AC-CL-184538
453900
(120)
Cycle 1 Day 7: CL-184538
242.0
(283)
21. Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody
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 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

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Cycle 1 Day 1: Total HP67.6 Antibody
2496
(210)
Cycle 1 Day 7: Total HP67.6 Antibody
14740
(388)
22. Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538
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 outcome measure.
Time Frame Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
AC-CL-184538
93490
(82)
CL-184538
247.8
(176)
23. Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody
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 outcome measure.
Time Frame Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 48
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour/milliliter]
3797
(135)
24. Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538
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 outcome measure.
Time Frame Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
AC-CL-184538
461500
(121)
CL-184538
1639
(181)
25. Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody
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 outcome measure.
Time Frame Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

Outcome Measure Data

Analysis Population Description
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/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 42
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour/milliliter]
26820
(131)
26. Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description 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)

Outcome Measure Data

Analysis Population Description
Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
TEAEs
49
96.1%
SAEs
34
66.7%
27. Secondary Outcome
Title 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
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 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)

Outcome Measure Data

Analysis Population Description
Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Count of Participants [Participants]
43
84.3%
28. Secondary Outcome
Title Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters
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 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)

Outcome Measure Data

Analysis Population Description
Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Count of Participants [Participants]
18
35.3%
29. Secondary Outcome
Title Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Description 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

Outcome Measure Data

Analysis Population Description
Immunogenicity analysis set included all participants in the safety analysis set who had at least 1 immunogenicity sample with results.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Treatment-induced ADA Positive
12.0
23.5%
Treatment-boosted ADA Positive
0.0
0%
30. Secondary Outcome
Title Percentage of Participants With Positive Neutralizing Antibodies (NAb)
Description 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

Outcome Measure Data

Analysis Population Description
Immunogenicity analysis set included all participants in the safety analysis set who had at least 1 immunogenicity sample with results.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 50
Number [percentage of participants]
2.0
3.9%
31. Secondary Outcome
Title Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)
Description 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)

Outcome Measure Data

Analysis Population Description
Full analysis set included all enrolled participants.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 51
Number (95% Confidence Interval) [percentage of participants]
9.8
19.2%
32. Secondary Outcome
Title Overall Survival (OS)
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. 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)

Outcome Measure Data

Analysis Population Description
Full analysis set included all enrolled participants.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
Measure Participants 51
Median (95% Confidence Interval) [months]
2.8

Adverse Events

Time Frame From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Adverse Event Reporting Description Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Gemtuzumab Ozogamicin (GO)
Arm/Group Description 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.
All Cause Mortality
Gemtuzumab Ozogamicin (GO)
Affected / at Risk (%) # Events
Total 45/50 (90%)
Serious Adverse Events
Gemtuzumab Ozogamicin (GO)
Affected / at Risk (%) # Events
Total 34/50 (68%)
Blood and lymphatic system disorders
Febrile Neutropenia 11/50 (22%)
Thrombocytopenia 2/50 (4%)
Anaemia 1/50 (2%)
Cardiac disorders
Atrial Fibrillation 1/50 (2%)
Supraventricular Tachycardia 1/50 (2%)
Eye disorders
Vitreous Floaters 1/50 (2%)
Gastrointestinal disorders
Gastric Haemorrhage 1/50 (2%)
General disorders
Disease Progression 5/50 (10%)
Pyrexia 3/50 (6%)
Multiple Organ Dysfunction Syndrome 1/50 (2%)
Infections and infestations
Sepsis 7/50 (14%)
Pneumonia 3/50 (6%)
Atypical Pneumonia 2/50 (4%)
Covid-19 Pneumonia 1/50 (2%)
Escherichia Urinary Tract Infection 1/50 (2%)
Eye Infection Fungal 1/50 (2%)
Neutropenic Sepsis 1/50 (2%)
Pneumonia Klebsiella 1/50 (2%)
Pneumonia Respiratory Syncytial Viral 1/50 (2%)
Sinusitis 1/50 (2%)
Injury, poisoning and procedural complications
Fall 1/50 (2%)
Traumatic Intracranial Haemorrhage 1/50 (2%)
Metabolism and nutrition disorders
Dehydration 1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia 1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure 1/50 (2%)
Vascular disorders
Capillary Leak Syndrome 1/50 (2%)
Other (Not Including Serious) Adverse Events
Gemtuzumab Ozogamicin (GO)
Affected / at Risk (%) # Events
Total 36/50 (72%)
Blood and lymphatic system disorders
Anaemia 5/50 (10%)
Febrile Neutropenia 9/50 (18%)
Neutropenia 5/50 (10%)
Thrombocytopenia 9/50 (18%)
Gastrointestinal disorders
Abdominal Pain Upper 3/50 (6%)
Constipation 5/50 (10%)
Diarrhoea 5/50 (10%)
Gingival Bleeding 3/50 (6%)
Nausea 8/50 (16%)
Vomiting 6/50 (12%)
General disorders
Asthenia 3/50 (6%)
Chills 3/50 (6%)
Fatigue 4/50 (8%)
Pyrexia 6/50 (12%)
Injury, poisoning and procedural complications
Infusion Related Reaction 3/50 (6%)
Investigations
Alanine Aminotransferase Increased 4/50 (8%)
Aspartate Aminotransferase Increased 5/50 (10%)
Gamma-Glutamyltransferase Increased 3/50 (6%)
Metabolism and nutrition disorders
Hypokalaemia 9/50 (18%)
Hypomagnesaemia 5/50 (10%)
Nervous system disorders
Headache 5/50 (10%)
Renal and urinary disorders
Acute Kidney Injury 3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis 5/50 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03727750
Other Study ID Numbers:
  • B1761031
  • 2018-002619-89
First Posted:
Nov 1, 2018
Last Update Posted:
Mar 25, 2022
Last Verified:
Feb 1, 2022