Phase 4
Completed N=51
Evaluating QTc, PK, Safety of Gemtuzumab Ozogamicin (GO) in Patients With CD33+ R/R AML
ECG · Pharmacokinetics · Safety
Source: ClinicalTrials.gov NCT03727750 ↗
Enrolled (actual)
51
Serious AEs
68.0%
Results posted
Mar 2022
Primary outcomePrimary: Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour — 4.90 milliseconds
◆ Published Evidence
Emerging
10citations · ~3 / year
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.
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.
Linked Publications
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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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 1 Hour |
4.90 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 2 Hours |
4.25 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 1: 4 Hours |
5.10 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 0 Hour |
-2.44 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 4: 2 Hours |
-0.45 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 0 Hour |
-1.00 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 2 Hours |
4.29 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 4 Hours |
4.19 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 1 Day 7: 6 Hours |
1.03 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 0 Hour |
4.0 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 1: 2 Hours |
7.3 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 0 Hour |
-5.4 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 2 Hours |
-1.6 | — |
| PRIMARY Change From Baseline in Corrected QT Interval for Heart Rate Using Fridericia's Formula (QTcF) at Cycle 2 Day 7: 6 Hours |
-8.8 | — |
| SECONDARY Clearance (CL) of Gemtuzumab Ozogamicin |
15.02; 4246; 0.3212 | — |
| SECONDARY Volume of Distribution of Gemtuzumab Ozogamicin |
— | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax): AC-CL-184538 and CL-184538 |
6457; 45.69; 11740; 58.76 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax): Total HP67.6 Antibody |
282.1; 585.6 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) |
2.080; 2.170; 2.080; 2.130; 3.920; 2.170 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): AC-CL-184538 and CL-184538 |
93260; 99.83; 453900; 242.0 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast): Total HP67.6 Antibody |
2496; 14740 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): AC-CL-184538 and CL-184538 |
93490; 247.8 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to Time 72 Hours (AUC0-72): Total HP67.6 Antibody |
3797 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): AC-CL-184538 and CL-184538 |
461500; 1639 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to Time 336 Hours (AUC0-336): Total HP67.6 Antibody |
26820 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
49; 34 | — |
| SECONDARY 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 |
43 | — |
| SECONDARY Number of Participants With Shift From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Laboratory Abnormalities- Chemistry Parameters |
18 | — |
| SECONDARY Percentage of Participants With Positive Anti-Drug Antibody (ADA) |
12.0; 0.0 | — |
| SECONDARY Percentage of Participants With Positive Neutralizing Antibodies (NAb) |
2.0 | — |
| SECONDARY Percentage of Participants Who Achieved Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi) |
9.8 | — |
| SECONDARY Overall Survival (OS) |
2.8 | — |
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).
Data sourced from ClinicalTrials.gov (NCT03727750) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.