Clinical trial NCT03727750: Evaluating QTc, PK, Safety of Gemtuzumab Ozogamicin (GO) in Patients With CD33+ R/R AML
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ECG
Pharmacokinetics
Safety
Keywords: gemtuzumab ozogamicin
Mylotarg
QT interval prolongation
Pharmacokinetics
Safety
Veno-occlusive disease
Anti-drug antibody
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-11-01
Enrollment: 51
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open-label, interventional
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour
timeFrame: Baseline, Cycle 1 Day 1: 1 Hour
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours
timeFrame: Baseline, Cycle 1 Day 1: 2 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours
timeFrame: Baseline, Cycle 1 Day 1: 4 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour
timeFrame: Baseline, Cycle 1 Day 4: 0 Hour
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours
timeFrame: Baseline, Cycle 1 Day 4: 2 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour
timeFrame: Baseline, Cycle 1 Day 7: 0 Hour
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours
timeFrame: Baseline, Cycle 1 Day 7: 2 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours
timeFrame: Baseline, Cycle 1 Day 7: 4 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours
timeFrame: Baseline, Cycle 1 Day 7: 6 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour
timeFrame: Baseline, Cycle 2 Day 1: 0 Hour
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours
timeFrame: Baseline, Cycle 2 Day 1: 2 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour
timeFrame: Baseline, Cycle 2 Day 7: 0 Hour
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours
timeFrame: Baseline, Cycle 2 Day 7: 2 Hours
measure: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours
timeFrame: Baseline, Cycle 2 Day 7: 6 Hours
Secondary outcomes:
measure: Clearance (CL) of Gemtuzumab Ozogamicin
timeFrame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
measure: Volume of Distribution of Gemtuzumab Ozogamicin
timeFrame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
measure: Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538
timeFrame: Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody
timeFrame: Pre dose, 1, 2, 4, 6, 24 and 72 hours post dose on Cycle 1 Day 1
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538
timeFrame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody
timeFrame: Pre dose, 2, 4, 6, 72, 192 and 336 hours post dose on Cycle 1 Day 7
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
measure: 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
timeFrame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
measure: Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters
timeFrame: From first dose of study drug up to 36 days after last dose (up to a maximum of 12 months)
measure: Percentage of Participants With Positive Anti-Drug Antibody (ADA)
timeFrame: From first dose of study drug up to maximum of 12 months
measure: Percentage of Participants With Positive Neutralizing Antibodies (NAb)
timeFrame: From first dose of study drug up to maximum of 12 months
measure: Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)
timeFrame: From first dose of study drug to 36 days after last dose (maximum up to of 12 months)
measure: Overall Survival (OS)
timeFrame: From the first dose of study treatment to the date of death or date of censored, whichever occurred first (maximum up to 12 months)
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta University Medical Center Clinical Research Pharmacy
state: Georgia
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Research Transition Facility
state: Alberta
city: Edmonton
country: Canada
facility: Kaye Edmonton Clinic
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, Juravinski Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Budapest
country: Hungary
facility: Semmelweis Egyetem I.sz Belgyogyaszati Klinika, Hematologiai Osztaly
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat - Hematologiai Osztaly
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Gdansk
country: Poland
facility: Klinika Hematologii i Transplantologii
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Wroclaw
country: Poland
facility: Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
city: Wroclaw
country: Poland
facility: Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch NHS Foundation Trust
state: Dorset
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Center NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: