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

University of Milano Bicocca112 enrolled

Overview

The purpose of this study is to assess the capability of the dPCR technique to predict the absence of disease relapses after imatinib discontinuation in CML patients with negative Q-RT-PCR results for longer than 18 months.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

112

Conditions

Chronic Myeloid Leukemia

Interventions

Imatinib mesylateDRUG

* Capsules, hard 50 or 100 mg/Film-coated Tablets 100 or 400 mg * Total dosage per day: 800 mg * Oral use

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (14)

McGill University - Jewish General Hospital Division of Hematology and Department of Oncology

Montreal, Quebec, Canada

Charité University of Berlin - Clinic of Medicine - Hematology and Oncology

Berlin, Germany

Outcomes

Primary Outcomes

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

Time frame: At 36 months.

Secondary Outcomes

Rate of molecular and cytogenetic relapse

Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled

Time frame: At 36 months

Rate of dPCR positive patients

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.

Time frame: At 36 months

Rate of dPCR negative patients

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.

Time frame: At 36 months

Rate of patients who are maintaining dPCR negativity for 36 months

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 frame: At 36 months

Time to molecular relapse

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.

Data from ClinicalTrials.gov

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