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

Completed

• Conditions: Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia; Chronic Phase Chronic Myelogenous Leukemia

• Registration Number: NCT03647215
• Lead Sponsor: Incyte Biosciences UK

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-18
• Study First Submitted: 2018-08-23
• Study First Submitted QC: 2018-08-23
• Study First Posted: 2018-08-27
• Primary Completion: 2021-03-31
• Study Completion: 2021-06-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-13
• Last Update Posted: 2021-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 427

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 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.
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.
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.
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.

Trial Locations

Locations (33)

Limerick University Hospital; 🇮🇪 Limerick, Dooradoyle, Ireland

University Hospital Waterford; 🇮🇪 Waterford, Ireland

Royal Cornwall Hospital; 🇬🇧 Truro, Cornwall, United Kingdom

Royal Devon & Exeter Hospital; 🇬🇧 Exeter, Devon, United Kingdom

Derriford Hospital; 🇬🇧 Plymouth, Devon, United Kingdom

Broomfield Hospital Chelmsford; 🇬🇧 Chelmsford, Essex, United Kingdom

Queen's Hospital; 🇬🇧 Romford, Essex, United Kingdom

Aberdeen Royal Infirmary; 🇬🇧 Aberdeen, Foresterhill, United Kingdom

Queen Alexandra Hospital; 🇬🇧 Portsmouth, Hampshire, United Kingdom

Medway Maritime Hospital; 🇬🇧 Gillingham, Kent, United Kingdom

Scroll for more (23 remaining)