Nilotinib in PH+, BCR-, ABL+ CML Patients (CML0811)

• Complete molecular response [ Time Frame: At 24 months of treatment ] [ Designated as safety issue: No ]
  To assess the complete molecular response (CMR4) rate at 24 months of treatment. For the purpose of this protocol, CMR is defined as a negative results of quantitative RT-PCR for BCR-ABL transcripts in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000, that corresponds to at least a 4-log reduction (hence, CMR4)
  
  

• Toxicity [ Time Frame: At three years from study entry ] [ Designated as safety issue: Yes ]
  Number of toxic events
  
  
• Compliance [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]
  Number of fully compliant patients and number of patients who do not comply with treatment
  
  
• The complete cytogenetic response (CCgR) rate [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ] [ Designated as safety issue: No ]
  
• The rate and the degree of molecular response [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ] [ Designated as safety issue: No ]
  
• The time to CCgR, the time to MMR and the time to CMR [ Time Frame: baseline ] [ Designated as safety issue: No ]
  
• Overall Survival (OS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
  From the date of the first nilotinib dose to death
  
  
• Progression Free Survival (PFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
  From the date of the first nilotinib dose to progression to AP or BP or death
  
  
• Failure Free Survival (FFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
  From the date of the first nilotinib dose to failure* or progression or death
  
  
• Event Free Survival (EFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
  From the date of the first nilotinib to any event. Including treatment discontinuation for adverse events, failure, progression to AP or BP, or death, whichever comes first.
  
  
• Patient-reported quality of life (QoL) [ Time Frame: At baseline and then at 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  

Drug: Nilotinib
Administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choise of the treatment will be up to the physician).

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administred orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choise of the treatment will be up to the physician).

Study duration is estimated in 6 years, 1 year of estimated enrollment, 2 years therapy duration. Thereafter, information on course and survival is due for other 3 years.

The main data analysis will be performed when all patients will complete 24 months of treatment (or discontinued earlier). Safety and tolerability profile will be assessed by collecting hematologic and non-hematologic adverse events, laboratory examinations and ECG data. The molecular response will be assessed using the GIMEMA standardized molecular laboratories (Labnet network).