Clinical study comparing treatment with nilotinib 600mg daily versus nilotinib 600 mg daily plus pegylated interferon-alpha 2a (PEG-IFN) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase de novo

INTERVENTION: Trade Name: Pegasys 135 microgrammes solution injectable. Product Name: Pegasys Pharmaceutical Form: Solution for injection INN or Proposed INN: PEGINTERFERON ALFA‐2A CAS Number: 198153‐51‐4 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 135‐ CONDITION: Chronic phase chronic myeloid leukaemia with Philadelphia chromosome positive or BCR‐ABL positive ; MedDRA version: 19.1 Level: PT Classification code 10034877 Term: Philadelphia chromosome positive System Organ Class: 10022891 ‐ Investigations ; MedDRA version: 19.1 Level: LLT Classification code 10052065 Term: Chronic phase chronic myeloid leukaemia System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] PRIMARY OUTCOME: Main Objective: The main objective of this test is to determine the molecular 4.5 cumulative response rate (RM 4.5) at 12 months and confirmed three months later after treatment with nilotinib compared to those induced by a combination of nilotinib + PEG‐low‐dose IFN in patients with CML in newly diagnosed chronic phase (<3 months). Primary end point(s): The primary endpoint of the study is the cumulative rate of patients RM 4.5 to 12 months, and confirmed at 15 months, analyzed by molecular biology centralized RT‐qPCR. The molecular response RM being defined by a 4.5 undetectable residual disease with a copy number of ABL or = 32 000 copies of a rate BCR‐ABL/ABL <0.0032% IS14. Secondary Objective: Compare between the 2 treatment groups:; 1 ‐ kinetics of obtaining RM 4.5 to 1 , 2, 3 , 6, 9 and 12 months and the stability of the RM 4.5 during the 2nd and 3rd year of treatment (15, 18, ??24, 30 and 36 months).; 2 ‐ The kinetics of obtaining RMM 1, 2 , 3, 6 , 9 and 12 months and the stability of the MMR during the 2nd and 3rd year of treatment (15, 18, ??24 , 30, and 36 months) .; 3 ‐ The rate of patients with a BCR‐ABL/ABL ( SI ) = 10 % at 3 and 6 months .; 4 ‐ The cumulative rate of complete cytogenetic response ( CCyR) at 3, 6 and 12 months.; 5 ‐ Tolerance (haematological adverse events and non ‐haematological ranking according to the NCI CTC AE v4) of the association nilotinib ‐PEG‐ IFN .; 6 ‐ the quality of life of treated patients.; 7 ‐ The rate of dose reduction or interruption of each treatment.; 8 ‐ The compliance to treatment in the 2 arms assessed by the Morisky questionnaire .; 9 ‐ The event‐free survival .; 10 ‐ Progression‐free survival .; 11 ‐ Overall survival .; Timepoint(s) of evaluation of this end point: 12 months INCLUSION CRITERIA: Chronic Myelogenous Leukemia ‐ Chronic phase positive to the Philadelphia chromosome or BCR‐ABL diagnosed less than 3 months prior to study entry Patient for whom treatment with Nilotinib is planned men and women patients age = 18 years ECOG score 0‐2 No other CML treatment except for hydroxyurea and/or anagrelide Without prior treatment with IFN or ITK (same for other purposes), AST and ALT <2.5 x ULN. Serum creatinine <2 x ULN No planned allogeneic stem cell transplantation Informed consent signed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200 SECONDARY OUTCOME: Secondary end point(s): 1 ‐ kinetics of obtaining RM 4.5 to 1 , 2, 3 , 6, 9 and 12 months and the stability of the RM 4.5 during the 2nd and 3rd year of treatment (15, 18, ??24, 30 and 36 months).; 2 ‐ The kinetics of obtaining RMM 1, 2 , 3, 6 , 9 and 12 months of nilotinib and the stability of the MMR during the 2nd and 3rd year of treatment (15, 18, ??24 , 30, and 36 months ) .; 3 ‐ The rate of patients with a BCR‐ABL/ABL ( SI ) = 10 % at 3 and 6 months .; 4 ‐ The cumulative rate of complete cytogenetic response ( CCyR) at 3, 6 and 12 months; 5 ‐ The deadline for obtaining the RMM (this period represents the interval between the date of initiation of nilotinib and the date of obtaining the MMR) .; 6 ‐ The deadline for obtaining the RM 4.5 (this period represents the interval between the date of initiation of nilotinib and the date of obtaining the RM 4.5 ) .; 7 ‐ The safety profile ( hematologic adverse events and non ‐haematological graded according to the NCI CTC AE v4); 8 ‐ The quality of life of treated patients; 9 ‐ The rate of dose reduction or interruption of each treatment and the mean daily doses of nilotinib and PEG ‐IFN administered.; 10 ‐ The compliance to treatment; 11 ‐ Event‐free survival .; 12 ‐ Progression‐free survival .; 13 ‐ Overall survival .; Timepoint(s) of evaluation of this end point: 36 months