Clinical trial NCT03647215: CALLS: CML and Ph+ALL Low Level Mutation Prevalence Survey
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-08-27
Enrollment: 427
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of participants with any mutation
timeFrame: Up to approximately 1 month per individual participant.
measure: Frequency of all specific mutations
timeFrame: Up to approximately 1 month per individual participant.
Secondary outcomes:
measure: Percentage of participants with individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML
timeFrame: Up to approximately 1 month per individual participant.
measure: Frequency of individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML
timeFrame: Up to approximately 1 month per individual participant.
measure: Percentage of participants with individual mutations in Ph+ ALL
timeFrame: Up to approximately 1 month per individual participant.
measure: Frequency of individual mutations in Ph+ ALL
timeFrame: Up to approximately 1 month per individual participant.
measure: Percentage of participants with individual mutations by whether a participant is intolerant or resistant to their previous TKI
timeFrame: Up to approximately 1 month per individual participant.
measure: Frequency of individual mutations by whether a patient is intolerant or resistant to their previous TKI
timeFrame: Up to approximately 1 month per individual participant.
measure: Percentage of participants with individual mutations by BCR-ABL level
timeFrame: Up to approximately 1 month per individual participant.
measure: Frequency of individual mutations by BCR-ABL level
timeFrame: Up to approximately 1 month per individual participant.
Other outcomes:
Locations:
city: Limerick
country: Ireland
facility: Limerick University Hospital
state: Dooradoyle
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
state: Devon
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital Chelmsford
state: Essex
city: Romford
country: United Kingdom
facility: Queen's Hospital
state: Essex
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Foresterhill
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
state: Hampshire
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
state: Kent
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: Lancashire
city: Manchester
country: United Kingdom
facility: Royal Oldham Hospital
state: Lancashire
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
state: Nottinghamshire
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: Suffolk
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust
state: West Midlands
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: West Midlands
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
state: West Smithfield
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: West Yorkshire
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: West Yorkshire
city: Airdrie
country: United Kingdom
facility: Monklands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital Wales
city: Croydon
country: United Kingdom
facility: Croydon University Hospital, Croydon Health Services NHS Trust
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS FT
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital, Cancer Centre, University Hospitals of North Midlands NHS Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital
Study officials:
affiliation: Incyte Biosciences UK
name: Michael Thompson, MD
role: STUDY_DIRECTOR
References: