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

NCT03647215 | Completed

• 1 other identifier: INCB 84344-401
• Study Type: observational
• Target: 427
• Locations: 2 countries
• Sites: 33

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.

Conditions

Chronic Phase Chronic Myelogenous Leukemia; Accelerated Phase Chronic Myelogenous Leukemia; Blastic 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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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.

• Percentage of participants with individual mutations in Ph+ ALL

  Up to approximately 1 month per individual participant.

• 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.

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Incyte Biosciences UK: lead

Study Sites (33)

Limerick University Hospital

Limerick, Dooradoyle, V94 F858, Ireland

Location

University Hospital Waterford

Waterford, X91 ER8E, Ireland

Location

Royal Cornwall Hospital

Truro, Cornwall, TR1 3LQ, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Broomfield Hospital Chelmsford

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Queen's Hospital

Romford, Essex, RM7 0AG, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Foresterhill, AB25 2ZN, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, Hampshire, PO6 3LY, United Kingdom

Location

Medway Maritime Hospital

Gillingham, Kent, ME75NY, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, Lancashire, FY3 8NR, United Kingdom

Location

Royal Oldham Hospital

Manchester, Lancashire, OL1 2JH, United Kingdom

Location

Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Ipswich Hospital

Ipswich, Suffolk, IP4 5PD, United Kingdom

Location

Heart of England NHS Foundation Trust

Birmingham, West Midlands, B9 5SS, United Kingdom

Location

Russells Hall Hospital

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

St Bartholomew's Hospital

London, West Smithfield, EC1A 7BE, United Kingdom

Location

Bradford Royal Infirmary

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

St James's University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Monklands Hospital

Airdrie, ML6 0JS, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

University Hospital Wales

Cardiff, CF14 4XW, United Kingdom

Location

Croydon University Hospital, Croydon Health Services NHS Trust

Croydon, CR7 7YE, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust

Middlesbrough, TS4 3BW, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX4 2PG, United Kingdom

Location

Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS FT

Sheffield, S10 2JF, United Kingdom

Location

Royal Stoke University Hospital, Cancer Centre, University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Study Officials

• Michael Thompson, MD

  Incyte Biosciences UK

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 27, 2018
• Study Start: December 18, 2017
• Primary Completion: March 31, 2021
• Study Completion: June 30, 2021
• Last Updated: August 16, 2021

Record last verified: 2021-08

Locations

GB (31); IE (2)