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

Blastic Phase Chronic Myelogenous Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03647215
• Other study ID #: INCB 84344-401
• Status: Completed
• Start date: December 18, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: August 2021
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 427
• Est. completion date: June 30, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Chronic Phase Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Philadelphia Chromosome
• Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
Ireland	Limerick University Hospital	Limerick	Dooradoyle
Ireland	University Hospital Waterford	Waterford
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Foresterhill
United Kingdom	Monklands Hospital	Airdrie
United Kingdom	Heart of England NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	Blackpool Victoria Hospital	Blackpool	Lancashire
United Kingdom	Bradford Royal Infirmary	Bradford	West Yorkshire
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	University Hospital Wales	Cardiff
United Kingdom	Broomfield Hospital Chelmsford	Chelmsford	Essex
United Kingdom	Croydon University Hospital, Croydon Health Services NHS Trust	Croydon
United Kingdom	Russells Hall Hospital	Dudley	West Midlands
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon & Exeter Hospital	Exeter	Devon
United Kingdom	Medway Maritime Hospital	Gillingham	Kent
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Ipswich Hospital	Ipswich	Suffolk
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Guy's Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	St Bartholomew's Hospital	London	West Smithfield
United Kingdom	Royal Oldham Hospital	Manchester	Lancashire
United Kingdom	The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust	Middlesbrough
United Kingdom	Queens Medical Centre	Nottingham	Nottinghamshire
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Queen Alexandra Hospital	Portsmouth	Hampshire
United Kingdom	Queen's Hospital	Romford	Essex
United Kingdom	Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS FT	Sheffield
United Kingdom	Royal Stoke University Hospital, Cancer Centre, University Hospitals of North Midlands NHS Trust	Stoke-on-Trent
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Biosciences UK

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with any mutation	All samples will be processed by NGS.	Up to approximately 1 month per individual participant.
Primary	Frequency of all specific mutations	All samples will be processed by NGS.	Up to approximately 1 month per individual participant.
Secondary	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.
Secondary	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.
Secondary	Percentage of participants with individual mutations in Ph+ ALL	All samples will be processed by NGS.	Up to approximately 1 month per individual participant.
Secondary	Frequency of individual mutations in Ph+ ALL	All samples will be processed by NGS.	Up to approximately 1 month per individual participant.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.