Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients

Randomized Multicenter Phase III Study Comparing the Rate of Molecular Response 4.5 at 12 Months in Newly Diagnosed Philadelphia Positive Chronic Phase Chronic Myelogenous Leukemia Patients Receiving Either Frontline Nilotinib 600 mg Daily or Nilotinib 600 mg Daily Combined to Pegylated Interferon-alfa 2a (Peg-IFN)

This is a phase III trial comparing, for newly diagnosed chronic phase CML patients, nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2 a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is the rate patients obtaining MR4.5 will be measured at this time point.

Inclusion Criteria:

• Male and female patients
• CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript), diagnosed less than 3 months prior to study entry
• Age of at least 18 years-old and less than 65 years
• Patient for whom treatment with Nilotinib is expected
• No other CML treatment except for hydroxyurea and/or anagrelide
• No previous TKI treatment.
• No previous treatment with IFN even for other purposes.
• SGOT and SGPT < 2.5 UNL
• Serum creatinine < 2 UNL
• No planned allogeneic stem cell transplantation
• Signed informed consent
• ECOG score 0 to 2

Exclusion Criteria:

• Contra-indication to IFN
• Transcripts other than M-Bcr
• Pregnancy, lactation
• HIV positivity, chronic hepatitis B or C.
• Prior or concurrent malignancy other than CML (exceptions to be mentioned)
• History of arterial occlusive disease or (peripheral, carotids or severe coronary heart disease).
• Permanent elevation of total cholesterol and triglycerides despite treatment
• Severe psychiatric/neurological disease (previous or ongoing)
• Concomitant auto-immune disease
• Other investigational product ongoing
• Ongoing immunosuppressive treatment
• Ongoing treatment at risk for inducing torsades de pointes
• QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…)
• Congenital long QTcF
• Unstabilised thyroid disorder
• No health insurance coverage