A Cohort Study To Establish the Prevalence of Mutations in Patients With CML Who Meet the ELN Criteria for Warning or Failure and Patients With Ph+ ALL With Detectable BCR-ABL Currently Being Treated With First or Subsequent TKI Therapy in the UK, Ireland, or France Using Next-Generation Sequencing

Incyte Biosciences UK33 sites in 2 countries427 target enrollmentDecember 18, 2017

ConditionsChronic Phase Chronic Myelogenous Leukemia Accelerated Phase Chronic Myelogenous Leukemia Blastic Phase Chronic Myelogenous Leukemia Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Chronic Phase Chronic Myelogenous Leukemia
Sponsor: Incyte Biosciences UK
Enrollment: 427
Locations: 33
Primary Endpoint: Percentage of participants with any mutation
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

A multicenter, prospective cohort study of the mutation status of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are being treated with first or subsequent tyrosine kinase inhibitor (TKI) therapy in the UK, Ireland, or France.

Registry

clinicaltrials.gov

Start Date

December 18, 2017

End Date

June 30, 2021

Last Updated

4 years ago

Study Type

Observational

Sex

All

Investigators

Sponsor

Incyte Biosciences UK

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Adult patients (age ≥ 18 years) with CML (in all phases of disease) or Ph+ ALL with detectable BCR-ABL levels who are being treated with a first or subsequent TKI.
•Patients with CML must meet the warning or failure criteria as per the ELN guidelines for first second and subsequent treatment line, including:
•BCR-ABL/ABL IS transcripts \> 10% at 3 months
•BCR-ABL/ABL IS transcripts \> 1% at 6 months
•BCR-ABL/ABL IS transcripts \> 0.1% at 12 months or later
•Patients with CML must not currently be in MMR (ie, have disease with BCR-ABL1/ABL1 transcripts \> 0.1% IS).
•Patients with Ph+ ALL with any level of BCR-ABL/ABL IS transcripts. Patients with Ph+ ALL should have BCR-ABL1/ABL1 transcript levels \> 0.1% and should not be currently enrolled in UKALL14 but may have relapsed during or after participation in UKALL
•Patients with an intermediate or high Sokal score (\> 0.8) can be recruited into the study from 3 months after diagnosis, irrespective of BCR-ABL1/ABL1 transcript levels at 3 months.
•Patients with additional chromosomal abnormalities at diagnosis and patients with AP-CML may be recruited into the study, irrespective of BCR-ABL1/ABL1 transcript levels at 3 months and beyond provided BCR-ABL1/ABL1 transcript levels are \> 0.1% IS. It is recommended that these patients have mutational analysis performed every 3 months irrespective of BCR-ABL1/ABL1 transcript levels until they reach MR3/MMR (BCR-ABL1/ABL1 \< 0.1% IS).
•Any patients who have previously undergone testing for KD mutations, irrespective of KD mutational analysis test results.

Exclusion Criteria

•Patients without detectable BCR-ABL and patients who have switched TKI due to intolerance but who have met the criteria for optimal response (CP-CML, ELN 2013 guidelines).

Outcomes

Primary Outcomes

Percentage of participants with any mutation

Time Frame: Up to approximately 1 month per individual participant.

All samples will be processed by NGS.

Frequency of all specific mutations

Time Frame: Up to approximately 1 month per individual participant.

All samples will be processed by NGS.

Secondary Outcomes

Frequency of individual mutations in Ph+ ALL(Up to approximately 1 month per individual participant.)
Percentage of participants with individual mutations by whether a participant is intolerant or resistant to their previous TKI(Up to approximately 1 month per individual participant.)
Percentage of participants with individual mutations by BCR-ABL level(Up to approximately 1 month per individual participant.)
Percentage of participants with individual mutations in Ph+ ALL(Up to approximately 1 month per individual participant.)
Frequency of individual mutations by whether a patient is intolerant or resistant to their previous TKI(Up to approximately 1 month per individual participant.)
Percentage of participants with individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML(Up to approximately 1 month per individual participant.)
Frequency of individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML(Up to approximately 1 month per individual participant.)
Frequency of individual mutations by BCR-ABL level(Up to approximately 1 month per individual participant.)