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

Sponsor
University of Milano Bicocca (Other)
Overall Status
Completed
CT.gov ID
NCT01578213
Collaborator
(none)
112
Enrollment
14
Locations
1
Arm
84.6
Duration (Months)
8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Imatinib mesylate
 Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
112 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients (ISAV)
Study Start Date :
Nov 9, 2011
Actual Primary Completion Date :
Nov 28, 2018
Actual Study Completion Date :
Nov 28, 2018

Arms and Interventions

Arm Intervention/Treatment
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

    		•

    Outcome Measures

    Primary Outcome Measures

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

    Secondary Outcome Measures

    1. Rate of molecular and cytogenetic relapse [At 36 months]

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

    2. Rate of dPCR positive patients [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.

    3. Rate of dPCR negative patients [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.

    4. Rate of patients who are maintaining dPCR negativity for 36 months [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.

    5. Time to molecular relapse [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.

    6. Overall Survival [At the end of the study]

      Overall Survival

    7. Quality of Life Assessment [At 36 months]

      Quality of Life, as measured by the Global Health Status\QOL and other subscales scores of EORTC-QLQ-C30 questionnaire

    8. Rate of patients progressing or developing resistance [At 36 months]

      Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • University of Milano Bicocca

    Investigators

    • 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: Arnon Nagler, MD, Chaim Sheba Medical Center
    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Milano Bicocca
    ClinicalTrials.gov Identifier:
    NCT01578213
    Other Study ID Numbers:
    • ISAV
    • 2011-002749-37
    First Posted:
    Apr 16, 2012
    Last Update Posted:
    Dec 3, 2019
    Last Verified:
    Nov 1, 2019
    Additional relevant MeSH terms:
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Imatinib Mesylate

    Study Results

    No Results Posted as of Dec 3, 2019