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

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

DRUG

Arsenic trioxide

DRUG

Idarubicin

DRUG

Cytarabine

DRUG

Tretinoin

DRUG

Mitoxantrone

DRUG

Mercaptopurine

DRUG

Methotrexate

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto

  collaborator OTHER

• Groupe Francophone des Myelodysplasies

  collaborator OTHER

• HOVON - Dutch Haemato-Oncology Association

  collaborator OTHER

• Programa para el Tratamiento de Hemopatías Malignas

  collaborator UNKNOWN

• German Federal Ministry of Education and Research

  collaborator OTHER_GOV

• Teva Pharmaceuticals Europe

  collaborator INDUSTRY

• Technische Universität Dresden

  lead OTHER

Principal Investigators

• Uwe Platzbecker, Prof. Dr. · Technische Universität Dresden (TUD)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2025-01-20

Completion

2025-01-20

Countries

• France
• Germany
• Italy
• Netherlands
• Spain