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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Participants<br>Participants with CML and Ph+ALL who are being treated with their first or subsequent TKI therapy. CML patients must meet the ELN criteria for warning and failure ) or have high SOKAL score (>0.8) or presence of additional chromosomal abnormalities (ACAs) and have detectable BCR-ABL levels. Ph+ALL patients need detectable BCR-ABL levels only. | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML | Participants in all phases of CML (CP, AP, and BP) will be enrolled. | 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 | Participants in all phases of CML (CP, AP, and BP) will be enrolled. | Up to approximately 1 month per individual participant. | 
| Percentage of participants with individual mutations in Ph+ ALL | All samples will be processed by NGS. | Up to approximately 1 month per individual participant. | 
| Frequency of individual mutations in Ph+ ALL | All samples will be processed by NGS. | 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 | All samples will be processed by NGS. | Up to approximately 1 month per individual participant. | 
| Frequency of individual mutations by whether a patient is intolerant or resistant to their previous TKI | All samples will be processed by NGS. | Up to approximately 1 month per individual participant. | 
| Percentage of participants with individual mutations by BCR-ABL level | 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. | Up to approximately 1 month per individual participant. | 
| Frequency of individual mutations by BCR-ABL level | 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. | Up to approximately 1 month per individual participant. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic myeloid leukemia, chronic phase, accelerated phase, blast phase, Philadelphia chromosome-positive acute lymphoblastic leukemia, tyrosine kinase inhibitor