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

Chronic Myeloid Leukemia Clinical Trial

— ISAV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01578213
• Other study ID #: ISAV
• Secondary ID: 2011-002749-37
• Status: Completed
• Phase: Phase 4
• Start date: November 9, 2011
• Est. completion date: November 28, 2018

Study information

• Verified date: November 2019
• Source: University of Milano Bicocca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: November 28, 2018
• Est. primary completion date: November 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

Drug:
• Imatinib mesylate
Capsules, hard 50 or 100 mg/Film-coated Tablets 100 or 400 mg Total dosage per day: 800 mg Oral use

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Countries where clinical trial is conducted

Canada,  Germany,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR	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	Rate of molecular and cytogenetic relapse	Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled	At 36 months
Secondary	Rate of dPCR positive patients	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
Secondary	Rate of dPCR negative patients	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
Secondary	Rate of patients who are maintaining dPCR negativity for 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
Secondary	Time to molecular relapse	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
Secondary	Overall Survival	Overall Survival	At the end of the study
Secondary	Quality of Life Assessment	Quality of Life, as measured by the Global Health Status\QOL and other subscales scores of EORTC-QLQ-C30 questionnaire	At 36 months
Secondary	Rate of patients progressing or developing resistance	Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled	At 36 months