NCT02688140

Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia

A Randomized Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA and Idarubicin Versus Standard ATRA and Anthracyclines-based Chemotherapy (AIDA Regimen) for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 135 (actual)
• Sponsor: Technische Universität Dresden · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) characterized by consistent clinical, morphologic, and genetic features. According to the FAB classification APL is designated as"M3 leukemia" and assigned to the WHO defined type of AML with recurrent cytogenetic abnormalities, "acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARα) and variants". Despite the dramatic progress achieved in frontline therapy of APL with ATRA plus anthracycline-based regimens, relapses still occur in approximately 20% of patients. Moreover, these regimens are associated with significant toxicities due to severe myelosuppression frequently associated with life-threatening infections and potentially serious late effects including development of secondary MDS/AML. In a recent randomized clinical trial in low/intermediate-risk APL (WBC ≤ 10 GPt/l APL0406 trial) a combination of arsenic trioxide (ATO) and ATRA has been shown to result into better survival with significantly lower toxicity rates compared to the standard ATRA + idarubicin (AIDA) therapy. Inspired by the results of this trial the investigators intend to perform a randomized study in high-risk APL (WBC at diagnosis \> 10 GPt/l) comparing standard AIDA-based treatment with ATO/ATRA combination including low-doses idarubicin during induction. The investigators propose a modified ATO/ATRA protocol with the addition of two doses of IDA (50% compared to standard AIDA induction) for induction because of the anticipated need of adding anthracyclines to control hyperleukocytosis and to achieve long-term disease control in this high-risk APL population. This is followed by 4 cycles of ATO/ATRA consolidation therapy. As in the APL0406 study for low/intermediate-risk patients the investigators expect less severe hematologic toxicity and treatment-related mortality resulting in an improved outcome for patients in the experimental arm. Furthermore, from the start of consolidation, these patients (in contrast to the standard arm) can be treated on an outpatient basis, which is also considered to be associated with an improved quality of life. The study will be conducted as a European intergroup study.

Conditions

• Acute Promyelocytic Leukemia

Interventions

Type	Name	Description
DRUG	Arsenic trioxide
DRUG	Idarubicin
DRUG	Cytarabine
DRUG	Tretinoin
DRUG	Mitoxantrone
DRUG	Mercaptopurine
DRUG	Methotrexate

Timeline

• Start date: 2016-06-01
• Primary completion: 2025-01-20
• Completion: 2025-01-20
• First posted: 2016-02-23
• Last updated: 2025-02-26

Locations

8 sites across 5 countries: France, Germany, Italy, Netherlands, Spain