CALLS: CML and Ph+ALL Low Level Mutation Prevalence Survey

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03647215

Enrollment

427

Registered

2018-08-27

Start date

2017-12-18

Completion date

2021-06-30

Last updated

2021-08-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Chronic myeloid leukemia, chronic phase, accelerated phase, blast phase, Philadelphia chromosome-positive acute lymphoblastic leukemia, tyrosine kinase inhibitor

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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). OR * 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 UKALL14. * 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. * Patients who have the ability to understand the requirements of the study and provide written informed consent.

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).

Design outcomes

Primary

Measure	Time frame	Description
Percentage of participants with any mutation	Up to approximately 1 month per individual participant.	All samples will be processed by NGS.
Frequency of all specific mutations	Up to approximately 1 month per individual participant.	All samples will be processed by NGS.

Secondary

Measure	Time frame	Description
Percentage of participants with individual mutations in Ph+ ALL	Up to approximately 1 month per individual participant.	All samples will be processed by NGS.
Frequency of individual mutations in Ph+ ALL	Up to approximately 1 month per individual participant.	All samples will be processed by NGS.
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.	All samples will be processed by NGS.
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.	Participants in all phases of CML (CP, AP, and BP) will be enrolled.
Percentage of participants with individual mutations by BCR-ABL level	Up to approximately 1 month per individual participant.	All samples will be processed by NGS. BCR-ABL levels defined as \> 0.1% to 1% international scale (IS), \> 1% to 10% IS, \> 10% IS.
Frequency of individual mutations by BCR-ABL level	Up to approximately 1 month per individual participant.	All samples will be processed by NGS. BCR-ABL levels defined as \> 0.1% to 1% international scale (IS), \> 1% to 10% IS, \> 10% IS.
Frequency of individual mutations by whether a patient is intolerant or resistant to their previous TKI	Up to approximately 1 month per individual participant.	All samples will be processed by NGS.
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.	Participants in all phases of CML (CP, AP, and BP) will be enrolled.

Countries

Ireland, United Kingdom

Outcome results