Identification of BCR::ABL1 Mutations by Digital PCR in CML

NCT ID: NCT07158294

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2029-04-01

Brief Summary

The goal of this study is to asses the ability of digital PCR (ddPCR) to detect actionable mutations in adult CML patients with failure of TKI therapy. The main objective of the study is it aims to answer is to assess whether ddPCR is at least as effective as NGS in detecting actionable (2GTKI-resistant) mutations.

To accomplish this aim, samples of participants treated according to clinical practice, will be taken and analyzed for the presence of BCR::ABL1 KD mutations by ddPCR.

Detailed Description

This is a multicenter biological study addressing the efficiency of ddPCR in detecting actionable mutations in patients with failure of TKI therapy. The study will involve 4 reference laboratories for BCR::ABL1 KD mutation testing Italian hematological centers enrolling patients and collecting samples for analysis.

Peripheral blood samples taken from patients treated according to clinical practice with resistance to imatinib or 2GTKI therapy according to the ELN recommendations will be shipped to one of the reference laboratories and analyzed by ddPCR using Bio-Rad ADS assays and reagents. Samples will be analyzed in batches of suitable size. ddPCR results will be compared with NGS results generated by reference laboratories belonging to LabNet CML network . In patients positive for mutations below 20% by ddPCR (low level mutations) peripheral blood sample(s) will be collected every 3 months at subsequent follow-up visits to monitor the kinetics of mutations in relation to therapy continuation or change.

No modification of TKI type or TKI dose will be performed on the basis of ddPCR results.

Conditions

Chronic Myeloid Leukemia (CML)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Evaluation of BCR::ABL1 KD mutations by ddPCR in CML patients resistant to TKI

Peripheral blood withdrawal for the analysis of BCR::ABL1 KD mutations by ddPCR. DdPCR results will be compared with NGS results.

Group Type: OTHER

Peripheral blood withdrawal for BCR::ABL1 mutations testing

Intervention Type: OTHER

Peripheral blood samples taken from patients treated according to clinical practice with resistance to imatinib or 2GTKI therapy according to the ELN recommendations will be shipped to one of the reference laboratories and analyzed by ddPCR using Bio-Rad ADS assays and reagents. Samples will be analyzed in batches of suitable size. ddPCR results will be compared with NGS results. In patients positive for mutations below 20% by ddPCR (low level mutations) peripheral blood sample(s) will be collected every 3 months at subsequent follow-up visits to monitor the kinetics of mutations in relation to therapy continuation or change.

Interventions

Peripheral blood withdrawal for BCR::ABL1 mutations testing

Peripheral blood samples taken from patients treated according to clinical practice with resistance to imatinib or 2GTKI therapy according to the ELN recommendations will be shipped to one of the reference laboratories and analyzed by ddPCR using Bio-Rad ADS assays and reagents. Samples will be analyzed in batches of suitable size. ddPCR results will be compared with NGS results. In patients positive for mutations below 20% by ddPCR (low level mutations) peripheral blood sample(s) will be collected every 3 months at subsequent follow-up visits to monitor the kinetics of mutations in relation to therapy continuation or change.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• molecularly confirmed diagnosis of BCR::ABL1+ CML;
• positivity for either e13a2 or e14a2 transcript;
• age ≥18 years;
• chronic phase;
• on therapy with imatinib or 2 GTKIs (dasatinib, nilotinib and bosutinib);
• candidate to TKI switch because of resistance according to the ELN recommendations OR with a confirmed warning response to 2GTKI therapy according to the ELN recommendations;
• Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion Criteria

• blastic phase;
• Previous allogeneic transplant or candidate to allogeneic transplant;
• on treatment with ponatinib or asciminib, investigational TKIs or non-TKI-therapy;
• switch performed or planned due to intolerance and not to resistance.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simona Soverini

Role: PRINCIPAL_INVESTIGATOR

Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy

Central Contacts

Paola Fazi

Role: CONTACT

p.fazi@gimema.it

00390670390528

Enrico Crea

Role: CONTACT

e.crea@gimema.it

00390670390514

Other Identifiers

CML1725

Identifier Type: -

Identifier Source: org_study_id