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

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Actual): 427

Contacts and Locations

Study Locations

• Ireland
  • Waterford, Ireland, X91 ER8E
    • University Hospital Waterford
  • Dooradoyle
    • Limerick, Dooradoyle, Ireland, V94 F858
      • Limerick University Hospital
• United Kingdom
  • Airdrie, United Kingdom, ML6 0JS
    • Monklands Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology centre
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital Wales
  • Croydon, United Kingdom, CR7 7YE
    • Croydon University Hospital, Croydon Health Services NHS Trust
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust
  • Oxford, United Kingdom, OX4 2PG
    • Oxford University Hospitals NHS Foundation Trust
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS FT
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital, Cancer Centre, University Hospitals of North Midlands NHS Trust
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LQ
      • Royal Cornwall Hospital
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon & Exeter Hospital
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Derriford Hospital
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 7ET
      • Broomfield Hospital Chelmsford
    • Romford, Essex, United Kingdom, RM7 0AG
      • Queen's Hospital
  • Foresterhill
    • Aberdeen, Foresterhill, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Queen Alexandra Hospital
  • Kent
    • Gillingham, Kent, United Kingdom, ME75NY
      • Medway Maritime Hospital
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
    • Manchester, Lancashire, United Kingdom, OL1 2JH
      • Royal Oldham Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Queens Medical Centre
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
      • Ipswich Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Heart of England NHS Foundation Trust
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
  • West Smithfield
    • London, West Smithfield, United Kingdom, EC1A 7BE
      • St Bartholomew's Hospital
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Bradford Royal Infirmary
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • St James's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Approximately 50 centers in the UK, Ireland and France that treat adult patients with CML and Ph+ ALL will be selected for participation in the study. The sites selected will be a mixture of hospital and academic centers.

The target study population will include adult patients with CML who meet the ELN criteria for warning or failure or have high SOKAL score > 0.8 or presence of additional chromosomal abnormalities (ACAs), all with detectable BCR-ABL levels. Ph+ ALL patients must have detectable BCR-ABL levels. Patients will be taking their first or subsequent TKI.

Consecutive patients within each prescriber's practice who meet the enrollment criteria and provide informed consent will be invited to enroll into the study.

Repeat NGS KD mutation testing is permitted under the protocol as deemed part of the standard management of patients.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
All Participants; 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?

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.

Collaborators and Investigators

• Sponsor: Incyte Biosciences UK
• Investigators: Study Director: Michael Thompson, MD, Incyte Biosciences UK

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2017
• Primary Completion (ACTUAL): March 31, 2021
• Study Completion (ACTUAL): June 30, 2021

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (ACTUAL): August 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 13, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; Chronic myeloid leukemia; chronic phase; Philadelphia chromosome-positive acute lymphoblastic leukemia; accelerated phase; blast phase
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Philadelphia Chromosome
• Other Study ID Numbers: INCB 84344-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Blood samples will be identifiable by a code consisting of numbers and initials. Samples may be stored and tested for up to 5 years after the completion of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No