Frontline Oral Arsenic Trioxide for APL

After initial eligibility screening, patients will be recruited to oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA) based-induction for 42 days. Daunorubicin or idarubicin will only be used during induction in patients <65 with presenting white blood cell count (WBC) ≥ 10 x 10^9/L. In patients not receiving daunorubicin, hydroxyurea if WBC ≥ 5 x 10^9/L within the first 14 days of induction. Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed weekly during induction. A reassessment bone marrow aspirate will be performed on day 28 of induction for assessment of morphologic remission.

Four weeks after the completion of induction phase, all patients, regardless of initial WBC, will receive two cycles of chemotherapy-free AAA consolidation (14 days every 28 days).

Four weeks after completion of consolidation, all patients will receive 12 cycles of chemotherapy-free AAA maintenance (14 days every 8 week).

Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed during every 4 weeks during consolidation, every 8 weeks during maintenance, and every 3 months for 24 months after completion of maintenance.

Inclusion criteria

• Newly diagnosed APL with t(15;17)(q24;q21) or acute myeloid leukaemia (AML) with variant RARA translocation according to the World Health Organization (WHO) Classification 2022
• Ability and willingness to comply with the study procedures and restrictions
• Voluntary written informed consent

Exclusion criteria

• ECOG performance score >2
• Decompensated heart failure with left-ventricular ejection fraction of less than 40% and global hypokinesia on echocardiogram.
• Prolonged corrected QT interval (QTc) ≥ 500ms, in the absence of electrolyte disturbances and medications known to prolong QTc
• Significant liver function derangement (Bilirubin > 3 times upper limit normal and/or ALT > 5 times upper limit of normal)
• Glomerular filtration rate (GRF) by Cockcroft-Gault formula or eGFR (MDRD) of less than 30mL/min in adults (aged ≥ 18) or Creatinine clearance < 50ml/min/1.73m2 in paediatric and adolescent patients (Age ≤ 17)
• Female subject who is lactating or has positive pregnancy test result prior to the first dose of study drug