Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients (ISAV)

• The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR [ Time Frame: At 36 months. ] [ Designated as safety issue: No ]
  The capability of the dPCR method to predict relapse-free patients relative to the standard method. NPV of each method will be computed as the number of patients who are negative according to either method at the time of imatinib discontinuation and remain relapse-free 36 months later over the total of negative patients according to either method, respectively
  
  

• Rate of molecular and cytogenetic relapse [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled
  
  
• Rate of dPCR positive patients [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Rate of patients who are dPCR positive before discontinuation of imatinib and who do not relapse within the following 36 months (false positive) out of the total number of relapse-free patients at month 36.
  
  
• Rate of dPCR negative patients [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Rate of patients who are dPCR negative before discontinuation of imatinib and who relapse (false negative) out of the total number of patients relapsing within the following 36 months.
  
  
• Rate of patients who are maintaining dPCR negativity for 36 months [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Rate of patients who are maintaining dPCR negativity for 36 months over the patients who are Q-RT-PCR negative at the end of the interval.
  
  
• Time to molecular relapse [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Time to molecular relapse, both from the first PCR-negative and from the discontinuation of imatinib to the time of loss of molecular response, respectively.
  
  
• Overall Survival [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]
  Overall Survival
  
  
• Quality of Life [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Quality of Life, as measured by the Global Health Status\QOL and other subscales scores of EORTC-QLQ-C30 questionnaire
  
  
• Rate of patients progressing or developing resistance [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
  Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled
  
  

This study will recruit approximately 100 CML patients under imatinib therapy in complete molecular remission with a history of at least 18 months of consecutive negative standard Q-RT-PCR as performed in their own centers. After signing the informed consent form (ICF), the patients will be tested for dPCR and will discontinue imatinib therapy. Then they will be monitored by standard Q-RT-PCR to assess the maintenance of the molecular remission; collection of data will be prospective as each center will collect the data for 36 months. At the end of this period, a peripheral blood sample for dPCR analysis will be obtained from those patients who will still have undetectable BCR-ABL transcripts by Q-RT-PCR to verify CML eradication. The maintenance of molecular remission by Q-RT-PCR and the survival will be monitored every six months during an additional follow-up of 24 months. Patients found to be positive to BCR-ABL transcripts by standard Q-RTPCR will repeat the test every 2 to 4 weeks until the loss of molecular remission, defined as two consecutive BCR-ABL positive tests with at least one with BCR-ABL/BCR value above 0.1%, or until the end of the study, whichever come first.