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

NCT03727750 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: B17610312018-002619-89
• Study Type: interventional
• Target: 51
• Locations: 6 countries
• Sites: 24

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.

Conditions

ECG; Pharmacokinetics; Safety

Keywords

gemtuzumab ozogamicin; Mylotarg; QT interval prolongation; Pharmacokinetics; Safety; Veno-occlusive disease; Anti-drug antibody

Outcome Measures

Primary Outcomes (14)

• Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour

  Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate. Change from baseline in QT interval corrected for heart rate using Fridericia's formula was reported.

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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 Outcomes (18)

• Clearance (CL) of Gemtuzumab Ozogamicin

  Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

• Volume of Distribution of Gemtuzumab Ozogamicin

  Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

• Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538

  Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

• Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody

  Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1; and Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7

Study Arms (1)

Gemtuzumab Ozogamicin (GO)

EXPERIMENTAL

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

Interventions

Gemtuzumab Ozogamicin DRUG

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

Gemtuzumab Ozogamicin (GO)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (24)

Augusta University Medical Center Clinical Research Pharmacy

Augusta, Georgia, 30912, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27834, United States

Location

Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Research Transition Facility

Edmonton, Alberta, T6G 2V2, Canada

Location

Kaye Edmonton Clinic

Edmonton, Alberta, T6G1Z1, Canada

Location

Hamilton Health Sciences, Juravinski Hospital

Hamilton, Ontario, L8V 1C3, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Semmelweis Egyetem I.sz Belgyogyaszati Klinika, Hematologiai Osztaly

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika

Debrecen, 4032, Hungary

Location

Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat - Hematologiai Osztaly

Győr, 9024, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Klinika Hematologii i Transplantologii

Gdansk, 80-214, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku

Wroclaw, 50-367, Poland

Location

Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego

Wroclaw, 50-369, Poland

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

The Royal Bournemouth and Christchurch NHS Foundation Trust

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

Belfast Health and Social Care Trust

Belfast, BT9 7AB, United Kingdom

Location

Clatterbridge Cancer Center NHS Foundation Trust

Liverpool, L7 8XP, United Kingdom

Location

Related Publications (1)

• Montesinos P, Kota V, Brandwein J, Bousset P, Benner RJ, Vandendries E, Chen Y, McMullin MF. A phase IV study evaluating QT interval, pharmacokinetics, and safety following fractionated dosing of gemtuzumab ozogamicin in patients with relapsed/refractory CD33-positive acute myeloid leukemia. Cancer Chemother Pharmacol. 2023 May;91(5):441-446. doi: 10.1007/s00280-023-04516-9. Epub 2023 Mar 9.

  PMID: 36892676 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Gemtuzumab

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, open-label, interventional

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: November 1, 2018
• Study Start: July 3, 2019
• Primary Completion: April 27, 2021
• Study Completion: April 27, 2021
• Last Updated: March 25, 2022
• Results First Posted: March 25, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share

Locations

US (4); CA (5); ES (4); GB (3); PL (4); HU (4)