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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01578213
Recruitment Status : Completed
First Posted : April 16, 2012
Last Update Posted : December 3, 2019
Information provided by (Responsible Party):
University of Milano Bicocca

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
Chronic Myeloid Leukemia 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.

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Study Type : Interventional  (Clinical Trial)
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 : November 9, 2011
Actual Primary Completion Date : November 28, 2018
Actual Study Completion Date : November 28, 2018

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 Name: Glivec, Gleevec

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Overall Survival [ Time Frame: At the end of the study ]
    Overall Survival

  7. 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

  8. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01578213

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Canada, Quebec
McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
Montréal, Quebec, Canada, H3T 1E2
Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
Berlin, Germany, 13353
Chaim Sheba Medical Center - Division of Hematology, BMT and CBB
Tel Hashomer, Israel, 52621
Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"
Catania, Italy/Catania, Italy, 95124
Università di Firenze Azienda Ospedaliera - Universitaria Careggi
Firenze, Italy/Firenze, Italy, 50134
Azienda Ospedaliera San Gerardo di Monza
Monza, Italy/MB, Italy, 20052
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia
Milano, Italy/Milano, Italy, 20162
IRCCS Policlinico San Matteo Pavia - Istituto di Ematologia
Pavia, Italy/Pavia, Italy, 27100
A.O. Bianchi-Melacrino-Morelli U.O. Ematologia
Reggio Calabria, Italy/Reggio Calabria, Italy, 89124
Universita di Tor Vergata Ospedale S. Eugenio
Rome, Italy/Rome, Italy, 00142
Ospedale S. Bortolo (USSL 6)
Vicenza, Italy/Vicenza, Italy, 36100
Ospedale Niguarda Ca' Granda - U.O. Ematologia
Milano, MI, Italy, 20162
IRCCS A.O.U. San Martino
Genova, Italy, 16132
Hospital Universitario Miguel Servet - Hematologia
Zaragoza, Spain
Sponsors and Collaborators
University of Milano Bicocca
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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 Universitario Miguel Servet
Principal Investigator: Micaela Bergamaschi, MD IRCCS A.O.U. San Martino
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Responsible Party: University of Milano Bicocca Identifier: NCT01578213    
Other Study ID Numbers: ISAV
2011-002749-37 ( EudraCT Number )
First Posted: April 16, 2012    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action