A Randomised Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA Versus Standard ATRA and Anthracycline-Based Chemotherapy (AIDA Regimen) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia
- Arm I:
- Induction therapy: Patients receive oral tretinoin twice daily and arsenic
trioxide IV over 2 hours on days 1-60. Patients achieving hematological complete
remission go on to receive consolidation therapy.
- Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-14.
Treatment with tretinoin repeats every 4 weeks for up to 7 courses. Patients also
receive arsenic trioxide IV over 2 hours on days 1-5 in weeks 1-4. Treatment with
arsenic trioxide repeats every 8 weeks for up to 4 courses.
- Arm II:
- Induction therapy: Patients receive tretinoin as in arm I induction therapy and
idarubicin IV over 20 minutes on days 2, 4, 6, and 8. Patients achieving
hematological complete remission go on to receive consolidation therapy.
- Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-45,
idarubicin IV over 20 minutes on days 1-4 and day 31, and mitoxantrone
hydrochloride IV over 30 minutes on days 16-20.
Marrow samples are collected after completion of consolidation therapy and analyzed by
reverse transcriptase-PCR for molecular remission. Patients achieving molecular remission
(PML-RARa negative) go on to receive maintenance therapy.
- Maintenance therapy: Patients receive oral mercaptopurine once daily and methotrexate
intramuscularly once weekly for 3 months. Treatment with mercaptopurine and
methotrexate repeats every 3 months for 7 courses. After completion of course 1 of
mercaptopurine and methotrexate, patients receive oral tretinoin once daily on days
1-15*. Treatment with tretinoin repeats every 3 months for 6 courses.
NOTE: *Patients do not receive mercaptopurine and methotrexate during tretinoin
After completion of study therapy, patients are followed periodically for 5 years.
As of 14th September 2010, all patients needed to evaluate the primary endpoint (162
patients) have been recruited but the trial accrual continued in order to assess one
secondary outcome (QoL)."
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
As of 14th september 2010, all patients needed to evaluate the primary endpoint have been recruited.
At maximum 3.5 years from study entry
Francesco Lo Coco, MD
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Italy: Ethics Committee