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

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.

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).