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

February 28, 2022 updated by: Pfizer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
      • Edmonton, Alberta, Canada, T6G1Z1
        • Kaye Edmonton Clinic
      • Edmonton, Alberta, Canada, T6G 2V2
        • Research transition Facility
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre
      • Hamilton, Ontario, Canada, L8V 1C3
        • Hamilton Health Sciences, Juravinski Hospital
  • Hungary
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem I.sz Belgyogyaszati Klinika, Hematologiai Osztaly
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika
      • Gyor, Hungary, 9024
        • Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat - Hematologiai Osztaly
      • Kaposvar, Hungary, 7400
        • Somogy Megyei Kaposi Mór Oktató Kórház
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne
      • Gdansk, Poland, 80-214
        • Klinika Hematologii i Transplantologii
      • Wroclaw, Poland, 50-367
        • Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
      • Wroclaw, Poland, 50-369
        • Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego
  • Spain
      • Barcelona, Spain, 08025
        • Hospital de La Santa Creu i Sant Pau
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
  • United Kingdom
      • Belfast, United Kingdom, BT9 7AB
        • Belfast Health And Social Care Trust
      • Liverpool, United Kingdom, L7 8XP
        • Clatterbridge Cancer Center NHS Foundation Trust
    • Dorset
      • Bournemouth, Dorset, United Kingdom, BH7 7DW
        • The Royal Bournemouth and Christchurch NHS Foundation Trust
  • United States
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Cancer Center at Augusta University
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center Clinical Research Pharmacy
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • Vidant Medical Center
      • Greenville, North Carolina, United States, 27834
        • Brody School of Medicine at East Carolina University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour
Time Frame: 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.
Baseline, Cycle 1 Day 1: 1 Hour
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 1: 2 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 1: 4 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour
Time Frame: 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.
Baseline, Cycle 1 Day 4: 0 Hour
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 4: 2 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour
Time Frame: 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.
Baseline, Cycle 1 Day 7: 0 Hour
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 7: 2 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 7: 4 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours
Time Frame: 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.
Baseline, Cycle 1 Day 7: 6 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour
Time Frame: 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.
Baseline, Cycle 2 Day 1: 0 Hour
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours
Time Frame: 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.
Baseline, Cycle 2 Day 1: 2 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour
Time Frame: 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.
Baseline, Cycle 2 Day 7: 0 Hour
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours
Time Frame: 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.
Baseline, Cycle 2 Day 7: 2 Hours
Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours
Time Frame: 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.
Baseline, Cycle 2 Day 7: 6 Hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clearance (CL) of Gemtuzumab Ozogamicin
Time Frame: 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.
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Volume of Distribution of Gemtuzumab Ozogamicin
Time Frame: 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.
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538
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
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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody
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
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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Time to Reach Maximum Observed Plasma Concentration (Tmax)
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
Tmax = time (hours) to maximum plasma concentration (Cmax).
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538
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
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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody
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
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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538
Time Frame: 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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody
Time Frame: 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.
Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538
Time Frame: 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.
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody
Time Frame: 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.
Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 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.
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Hematology and Coagulation Parameters
Time Frame: 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.
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters
Time Frame: 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.
From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Time Frame: 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.
From first dose of study drug up to maximum of 12 months
Percentage of Participants With Positive Neutralizing Antibodies (NAb)
Time Frame: 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.
From first dose of study drug up to maximum of 12 months
Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)
Time Frame: 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.
From first dose of study drug to 36 days after last dose (maximum up to of 12 months)
Overall Survival (OS)
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)
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.
From the first dose of study treatment to the date of death or date of censored, whichever occurred first (maximum up to 12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 3, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 27, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 27, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 28, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B1761031
  • 2018-002619-89 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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