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

Phase 4
18 Years
Open (Enrolling)
Chronic Myeloid Leukemia

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Trial Information

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.

Inclusion Criteria:

1. Signed and dated IRB/IEC-approved Informed Consent

2. Age>=18 years

3. Male or female patients with CML diagnosed in chronic or accelerated phase and who
have been treated for more than 2 consecutive years with imatinib therapy

4. Sustained Complete Molecular Response (as defined by the treating center) for at
least 18 months with imatinib treatment

5. A minimum of 3 CMR determined by Q-RT-PCR analysis to support disease status, with
the list one performed within 3 calendar months prior to enrollment date

6. Willingness and ability to comply with scheduled visits laboratory tests and other
study procedures

Exclusion Criteria:

1. Allogenic hematopoietic stem cell transplantation

2. Known active infections including human immunodeficiency virus (HIV) positivity

3. Current enrollment another clinical trial

4. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration or may interfere with the interpretation of study results

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR

Outcome Description:

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

Outcome Time Frame:

At 36 months.

Safety Issue:


Principal Investigator

Carlo Gambacorti-Passerini, MD

Investigator Role:

Study Director

Investigator Affiliation:

Azienda Ospedaliera San Gerardo di Monza


Italy: The Italian Medicines Agency/Coordinating Site Administration

Study ID:




Start Date:

November 2011

Completion Date:

November 2018

Related Keywords:

  • Chronic Myeloid Leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive