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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Milano Bicocca
ClinicalTrials.gov Identifier:
NCT01578213
First received: April 13, 2012
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Chronic Myeloid Leukemia
Drug: Imatinib mesylate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients (ISAV)

Resource links provided by NLM:


Further study details as provided by University of Milano Bicocca:

Primary Outcome Measures:
  • The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR [ Time Frame: At 36 months. ] [ Designated as safety issue: No ]
    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:
  • Rate of molecular and cytogenetic relapse [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled

  • Rate of dPCR positive patients [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    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.

  • Rate of dPCR negative patients [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    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.

  • Rate of patients who are maintaining dPCR negativity for 36 months [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    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 to molecular relapse [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]
    Overall Survival

  • Quality of Life [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    Quality of Life, as measured by the Global Health Status\QOL and other subscales scores of EORTC-QLQ-C30 questionnaire

  • Rate of patients progressing or developing resistance [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled


Estimated Enrollment: 100
Study Start Date: November 2011
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01578213

Locations
Canada, Quebec
McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
Montréal, Quebec, Canada, H3T 1E2
Germany
Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
Berlin, Germany, 13353
Israel
Chaim Sheba Medical Center - Division of Hematology, BMT and CBB
Tel Hashomer, Israel, 52621
Italy
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
Netherlands
Onze Lieve Vrouwe - Haematology/Oncology
Amsterdam, Netherlands
Spain
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: Anna D'Emilio, 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: Ester Orlandi, 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: Enrica Morra, 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: Pilar Giraldo, MD Hospital Universitario Miguel Servet
Principal Investigator: Ivana Pierri, MD IRCCS A.O.U. San Martino
  More Information

No publications provided

Responsible Party: University of Milano Bicocca
ClinicalTrials.gov Identifier: NCT01578213     History of Changes
Other Study ID Numbers: ISAV, 2011-002749-37
Study First Received: April 13, 2012
Last Updated: May 14, 2014
Health Authority: Italy: The Italian Medicines Agency/Coordinating Site Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014