International Pediatric Study of Arsenic Trioxide and Tretinoin ± Gemtuzumab Ozogamicin for Acute Promyelocytic Leukemia in Children and Adolescents

The primary objective of this study is to assess the efficacy, defined by event-free survival, of a combination of arsenic trioxide and all-trans retinoic acid in children and adolescents with newly diagnosed standard-risk acute promyelocytic leukemia. Additionally, the study aims to evaluate the safety and efficacy of a combination therapy consisting of arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in patients with high-risk acute promyelocytic leukemia.

Secondary objectives include:

• Evaluation of the short- and long-term toxicity profile of arsenic trioxide when combined with all-trans retinoic acid or gemtuzumab ozogamicin.
• Comparison of minimal residual disease clearance kinetics with previous protocols.
• Estimation of the cumulative incidence of molecular relapse and hematological relapse.
• Calculation of the overall survival probability and the early death rate.
• Prospective evaluation of the impact of the FLT3-ITD mutation in this population.
• Comparison of quality of life and the duration of hospitalization relative to prior protocols.

The sponsor did not provide information regarding the total number of participants. The study population consists of children and adolescents diagnosed with acute promyelocytic leukemia. Participants include both male and female individuals under the age of 18 years. Inclusion requires a new diagnosis confirmed by the presence of the PML/RARα fusion gene. For female participants of child-bearing potential, a negative beta-HCG test is required. These individuals must adhere to specific conduct to avoid procreation during the study and for three months following the final dose of medication.

This phase II clinical study is designed to evaluate the efficacy and safety of various therapeutic interventions in children and adolescents with acute promyelocytic leukemia. The primary objective is to assess event-free survival in newly diagnosed standard-risk patients using a combination of arsenic trioxide and all-trans retinoic acid. Additionally, the study explores the efficacy and safety of a combination therapy including gemtuzumab ozogamicin for high-risk cases. Investigational treatments involve cytarabine, methotrexate, methylprednisolone, and tretinoin administered through intravenous use, intrathecal use, or oral use. The research period is estimated to extend from October 2019 to October 2027. Participation involves a screening process to confirm the presence of the PML/RARα fusion gene and verify age requirements. The study includes induction therapy, consolidation cycles, and subsequent follow-up to monitor hematological complete remission and molecular remission. Monitoring includes the assessment of toxicity and overall survival. Early termination may occur based on clinical requirements or safety considerations.

Arsenic trioxide is administered as a solution for infusion via intravenous use at a dosage of 0.15 mg/kg. This experimental treatment is utilized in the management of acute promyelocytic leukemia.

Tretinoin is provided in the soft capsule pharmaceutical form for oral use. The prescribed dosage is 25 mg/m².

Gemtuzumab ozogamicin is administered as a solution for infusion via intravenous use at a dosage of 3 mg/m².

Cytarabine is administered through intrathecal use at a dosage of 30 mg. The pharmaceutical forms include solution for injection and solution for injection/infusion.

Methotrexate is administered via intrathecal use at a dosage of 12 mg. Available pharmaceutical forms include solution for injection and solution for infusion.

Methylprednisolone is administered through intrathecal use at a dosage of 10 mg. The pharmaceutical forms include suspension for injection and solution for injection containing methylprednisolone sodium succinate.

The primary efficacy endpoint for this study in children and adolescents with acute promyelocytic leukemia is event-free survival (EFS). This cumulative endpoint is defined by the following events: failure to achieve hematological complete remission after induction therapy, failure to achieve molecular remission after three consolidation courses (molecular resistance), relapse (hematological or molecular), and death, including early death, within two years from diagnosis.

Secondary efficacy parameters include:

• The rate of hematological complete remission after induction.
• The rate of early and aplastic death during induction.
• Overall survival (OS).
• The cumulative incidence of relapse (CIR) for both hematological and molecular relapse.
• Minimal residual disease (MRD) clearance kinetics.
• The rate of molecular remission after three consolidation cycles.
• The reduction of PML/RARα transcript levels during treatment.