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

November 28, 2019 updated by: University of Milano Bicocca

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
112

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H3T 1E2
        • McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
  • Germany
      • Berlin, Germany, 13353
        • Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
  • Israel
      • Tel Hashomer, Israel, 52621
        • Chaim Sheba Medical Center - Division of Hematology, BMT and CBB
  • Italy
      • Genova, Italy, 16132
        • IRCCS A.O.U. San Martino
    • Italy/Catania
      • Catania, Italy/Catania, Italy, 95124
        • Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"
    • Italy/Firenze
      • Firenze, Italy/Firenze, Italy, 50134
        • Università di Firenze Azienda Ospedaliera - Universitaria Careggi
    • Italy/MB
      • Monza, Italy/MB, Italy, 20052
        • Azienda Ospedaliera San Gerardo di Monza
    • Italy/Milano
      • Milano, Italy/Milano, Italy, 20162
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia
    • Italy/Pavia
      • Pavia, Italy/Pavia, Italy, 27100
        • IRCCS Policlinico San Matteo Pavia - Istituto di Ematologia
    • Italy/Reggio Calabria
      • Reggio Calabria, Italy/Reggio Calabria, Italy, 89124
        • A.O. Bianchi-Melacrino-Morelli U.O. Ematologia
    • Italy/Rome
      • Rome, Italy/Rome, Italy, 00142
        • Universita di Tor Vergata Ospedale S. Eugenio
    • Italy/Vicenza
      • Vicenza, Italy/Vicenza, Italy, 36100
        • Ospedale S. Bortolo (USSL 6)
    • MI
      • Milano, MI, Italy, 20162
        • Ospedale Niguarda Ca' Granda - U.O. Ematologia
  • Spain
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet - Hematologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Imatinib
Drug: Imatinib mesylate
  • Capsules, hard 50 or 100 mg/Film-coated Tablets 100 or 400 mg
  • Total dosage per day: 800 mg
  • Oral use
Other Names:
  • Glivec, Gleevec

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR
Time Frame: At 36 months.
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.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of molecular and cytogenetic relapse
Time Frame: At 36 months
Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled
At 36 months
Rate of dPCR positive patients
Time Frame: At 36 months
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.
At 36 months
Rate of dPCR negative patients
Time Frame: At 36 months
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.
At 36 months
Rate of patients who are maintaining dPCR negativity for 36 months
Time Frame: At 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.
At 36 months
Time to molecular relapse
Time Frame: At 36 months
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.
At 36 months
Overall Survival
Time Frame: At the end of the study
Overall Survival
At the end of the study
Quality of Life Assessment
Time Frame: At 36 months
Quality of Life, as measured by the Global Health Status\QOL and other subscales scores of EORTC-QLQ-C30 questionnaire
At 36 months
Rate of patients progressing or developing resistance
Time Frame: At 36 months
Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled
At 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Milano Bicocca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Carlo Gambacorti-Passerini, MD, Azienda Ospedaliera San Gerardo di Monza
  • Principal Investigator: Eros Di Bona, MD, Ospedale S. Bortolo (USSL 6)
  • Principal Investigator: Francesco Di Raimondo, MD, Azienda Ospedaliero-Universitaria "Policlinico - Vittorio Emanuele"
  • Principal Investigator: Elisabetta Abruzzese, MD, Università di Tor Vergata Ospedale di S. Eugenio
  • Principal Investigator: Luca Arcaini, MD, IRCCS Policlinico San Matteo Pavia
  • Principal Investigator: Valeria Santini, MD, Università di Firenze Azienda Ospedaliera-Universitaria Careggi
  • Principal Investigator: Bruno Martino, MD, A.O. Bianchi-Melacrino-Morelli
  • Principal Investigator: Alessandra Iurlo, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
  • Principal Investigator: Ester Pungolino, MD, Ospedale Niguarda Ca' Granda
  • Principal Investigator: Philipp le Coutre, MD, Charité University of Berlin
  • Principal Investigator: Sarit Assouline, MD, McGill University - Jewish General Hospital
  • Principal Investigator: Onno Leeskma, MD, Onze Lieve Vrouwe Gasthuis
  • Principal Investigator: Marcio Andrade, MD, Hospital Miguel Servet
  • Principal Investigator: Micaela Bergamaschi, MD, IRCCS A.O.U. San Martino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 9, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 28, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 28, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 3, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISAV
  • 2011-002749-37 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings