PONATINIB-3001

Primary Objectives
The primary objective of the study is to compare the efficacy of ponatinib versus imatinib, administered as first-line therapy in combination with reduced-intensity chemotherapy, in patients
with newly diagnosed Ph+ ALL, as measured by the MRD-negative CR rate at the end of induction (see Table 13.a for the definitions of MRD negativity and CR).

Secondary Objectives
The key secondary objective is to compare the rates of EFS between the 2 cohorts.
Other secondary objectives are:
 To compare the rates of CR and incomplete CR (CRi) between the 2 cohorts, at the end of
Cycle 1, the end of Cycle 2, and the end of induction.
 To compare the rates of MR3, MRD negativity (MR4), and MR4.5 between the 2 cohorts, at the end of Cycle 1, the end of Cycle 2, and the end of induction.
 To compare the rates of primary induction failure (PIF) and overall response rate (ORR)
between the 2 cohorts, at the end of induction.
 To determine the duration of MRD-negative CR in each of the 2 cohorts.
 To compare the rate of MR4.5 between the 2 cohorts, at multiple intervals after the end of
induction, including best response.
 To determine the duration of CR in each of the 2 cohorts.
 To compare the time to treatment failure between the 2 cohorts.
 To compare the duration of MR4.5 between the 2 cohorts, in patients who achieved MR4.5.
 To compare outcomes in patients with and without HSCT, between the 2 cohorts.
 To compare the rates of OS between the 2 cohorts.

Safety Objectives
The safety objectives are:
 To characterize the rates of AEs/SAEs, AOEs, venous thrombotic/embolic events (VTEs), and other safety outcomes of interest in the 2 cohorts, using multiple methods.
 To compare the tolerability between the 2 cohorts, including the rates of discontinuation, dose reductions, and dose interruptions due to AEs.

Exploratory Objectives
The exploratory objectives are:
 To compare patient-reported quality of life (Functional Assessment of Cancer Therapy – Leukemia [FACT-Leu] and EuroQOL-5 Dimension-5 Level [EQ-5D-5L]) results between the 2 cohorts.
 To compare medical resource utilization (MRU) results between the 2 cohorts.
 To compare the time to start of alternative therapy between the 2 cohorts.
 To compare the time to HSCT between the 2 cohorts.
 To explore biomarkers of disease sensitivity and resistance to ponatinib and imatinib. Voir le protocole 􀀀 Histoire médicale
􀀀 Poids et taille
􀀀 Examen physique
􀀀 Signes vitaux
􀀀 Échocardiogramme
􀀀 Électrocardiogramme
􀀀 Examen de la vue
􀀀 Prises de sang
􀀀 Questionnaires : (symptômes éprouvés, qualité de vie)

méthodologie
Ceci est une étude randomisée ouverte. Les patients sont donc randomisés 2:1 soit dans le bras ponatinib + chimiotherapie à
intensité réduite ou imatinib + chimiothérapie à intensité réduite. Les patients recevront le traitement temps et aussi longtemps
qu’ils en perçoivent un bénéfice.