Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients (ISAV)
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR
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
At 36 months.
Carlo Gambacorti-Passerini, MD
Azienda Ospedaliera San Gerardo di Monza
Italy: The Italian Medicines Agency/Coordinating Site Administration