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

NCT ID: NCT03727750

Last Updated: 2022-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-03
• Study Completion Date: 2021-04-27

Brief Summary

This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc, pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and pediatric patients with relapsed or refractory CD33-positive AML.

Detailed Description

This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc, pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and pediatric patients with relapsed or refractory CD33-positive AML. Approximately 50 adult (age >=18 years) and 6 pediatric (12 years =< age =< 17 years) patients who satisfy the study eligibility criteria will be enrolled. Enrolled patients will receive GO 3 mg/m2 up to 2 cycles on Days 1, 4, and 7 at each cycle. The impact of GO on VOD/SOS in the context of previous and subsequent HSCT will also be assessed. Patients enrolled in the study will receive three doses of GO 3 mg/m2 (up to one vial) as a 2-hour intravenous infusion on Cycle 1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7 will be allowed at the investigator's discretion for patients who meet the following criteria after Cycle 1: Bone marrow with a decrease of blast percentage to at least 25% or a decrease of pretreatment blast percentage by at least 50%; and Blood count with neutrophils >=1,000/µL, and platelets >=50,000/µL, except in patients with the bone marrow blasts >=5%, the decrease in neutrophils and platelets thought to be due to the underlying leukemia. After GO treatment, subsequent anticancer therapy such as consolidation or conditioning regimen and/or HSCT could be considered at the investigator's discretion. A minimum interval of 2 months is recommended between the last dose of GO and HSCT.

Conditions

ECG; Pharmacokinetics; Safety

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Gemtuzumab Ozogamicin

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Augusta University Medical Center Clinical Research Pharmacy

Augusta, Georgia, United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Vidant Medical Center

Greenville, North Carolina, United States

University of Alberta Hospital

Edmonton, Alberta, Canada

Research Transition Facility

Edmonton, Alberta, Canada

Kaye Edmonton Clinic

Edmonton, Alberta, Canada

Hamilton Health Sciences, Juravinski Hospital

Hamilton, Ontario, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Semmelweis Egyetem I.sz Belgyogyaszati Klinika, Hematologiai Osztaly

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika

Debrecen, , Hungary

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

Győr, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

Klinika Hematologii i Transplantologii

Gdansk, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego

Wroclaw, , Poland

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

The Royal Bournemouth and Christchurch NHS Foundation Trust

Bournemouth, Dorset, United Kingdom

Belfast Health and Social Care Trust

Belfast, , United Kingdom

Clatterbridge Cancer Center NHS Foundation Trust

Liverpool, , United Kingdom

Countries

United States; Canada; Hungary; Poland; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36892676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=B1761031

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

Other Identifiers

2018-002619-89

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B1761031

Identifier Type: -

Identifier Source: org_study_id