Clinical trial NCT01578213: Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients
Official title: Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients (ISAV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Myeloid Leukemia
Lead sponsor: University of Milano Bicocca
Sponsor class: OTHER
First posted: 2012-04-16
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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 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

Primary outcomes:
measure: The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR
timeFrame: At 36 months.
Secondary outcomes:
measure: Rate of molecular and cytogenetic relapse
timeFrame: At 36 months
measure: Rate of dPCR positive patients
timeFrame: At 36 months
measure: Rate of dPCR negative patients
timeFrame: At 36 months
measure: Rate of patients who are maintaining dPCR negativity for 36 months
timeFrame: At 36 months
measure: Time to molecular relapse
timeFrame: At 36 months
measure: Overall Survival
timeFrame: At the end of the study
measure: Quality of Life Assessment
timeFrame: At 36 months
measure: Rate of patients progressing or developing resistance
timeFrame: At 36 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
state: Quebec
city: Berlin
country: Germany
facility: Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center - Division of Hematology, BMT and CBB
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"
state: Italy/Catania
city: Firenze
country: Italy
facility: Università di Firenze Azienda Ospedaliera - Universitaria Careggi
state: Italy/Firenze
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Italy/MB
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia
state: Italy/Milano
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo Pavia - Istituto di Ematologia
state: Italy/Pavia
city: Reggio Calabria
country: Italy
facility: A.O. Bianchi-Melacrino-Morelli U.O. Ematologia
state: Italy/Reggio Calabria
city: Rome
country: Italy
facility: Universita di Tor Vergata Ospedale S. Eugenio
state: Italy/Rome
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo (USSL 6)
state: Italy/Vicenza
city: Milano
country: Italy
facility: Ospedale Niguarda Ca' Granda - U.O. Ematologia
state: MI
city: Genova
country: Italy
facility: IRCCS A.O.U. San Martino
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet - Hematologia
Study officials:
affiliation: Azienda Ospedaliera San Gerardo di Monza
name: Carlo Gambacorti-Passerini, MD
role: STUDY_DIRECTOR
affiliation: Ospedale S. Bortolo (USSL 6)
name: Eros Di Bona, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliero-Universitaria "Policlinico - Vittorio Emanuele"
name: Francesco Di Raimondo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università di Tor Vergata Ospedale di S. Eugenio
name: Elisabetta Abruzzese, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Policlinico San Matteo Pavia
name: Luca Arcaini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università di Firenze Azienda Ospedaliera-Universitaria Careggi
name: Valeria Santini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Bianchi-Melacrino-Morelli
name: Bruno Martino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Alessandra Iurlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chaim Sheba Medical Center
name: Arnon Nagler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Niguarda Ca' Granda
name: Ester Pungolino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité University of Berlin
name: Philipp le Coutre, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University - Jewish General Hospital
name: Sarit Assouline, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Onze Lieve Vrouwe Gasthuis
name: Onno Leeskma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Marcio Andrade, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS A.O.U. San Martino
name: Micaela Bergamaschi, MD
role: PRINCIPAL_INVESTIGATOR
References: