Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia
Status:
Recruiting
Trial end date:
2022-01-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Technische Universität Dresden
Collaborators:
German Federal Ministry of Education and Research Groupe Francophone des Myelodysplasies Gruppo Italiano Malattie EMatologiche dell'Adulto Haemato Oncology Foundation for Adults in the Netherlands HOVON - Dutch Haemato-Oncology Association Programa para el Tratamiento de Hemopatías Malignas Teva Pharmaceuticals Europe