Gene Expression Profiles in CML Non-responders

January 3, 2020 updated by: Sheffield Children's NHS Foundation Trust

Detecting Expression Profiles Associated With Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia Patients Without Detectable Tyrosine Kinase Domain Mutations, Using Transcriptomics

Chronic myeloid leukaemia (CML) is a haematological malignancy primarily driven by the fusion oncogene BCR-ABL1, resulting in a constitutively expressed tyrosine kinase. CML is treated very effectively by the tyrosine kinase inhibitors (TKIs) resulting in almost undetectable levels of disease. However, some patients show resistance to first line treatment, requiring second and third generation TKIs. Such resistance is due to the presence of tyrosine kinase domain (TKD) mutations, however TKDs do not appear to be present in all patients who do not respond to treatment.

The aim of this project is to utilise gene expression arrays to identify transcriptomic profiles associated with resistance to TKIs in the absence of a demonstrable TKD mutation. The presence of such profiles may allow for a more targeted approach to treatment, if non-responders can be identified earlier in the disease management pathway. Being able to predict those that will not respond to first line treatment will allow for better stratification of patients.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The aim of this project is to use gene expression microarrays to detect expression profiles which may be associated with TKI resistance in order to better stratify CML patients and allow a more targeted approach to therapy. The project may also help elucidate the mechanism of resistance in those without a discernible TKD mutation. Ultimately it is hoped that this would lead to larger studies which could improve the clinical pathway for CML patients without TKD mutations.

Some previous studies have studied the gene expression profile of CML patients demonstrating resistance to TKIs, using Affymetrix arrays. However, none of these appear to have specifically investigated non-responders with and without a TKD mutation.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2TH
        • Clinical Research Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 85 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

CML patients with poor response to TKIs as identified through routine clinical testing at SDGS, either with or without a tyrosine kinase domain mutation as tested for by mutational analysis.

Description

Inclusion Criteria:

  • CML patients with poor response to TKIs as identified through routine clinical testing at SDGS, either with or without a tyrosine kinase domain mutation as tested for by mutational analysis.

Exclusion Criteria:

  • Any samples that do not meet the above inclusion criteria, but particularly not CML patients with an optimal response to TKIs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Success identification of at least 5 markers of resistance in patients without a TKD mutation and confirmation of their expression levels using qPCR
Time Frame: 2 months
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Children's NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2017

Primary Completion (Actual)

May 4, 2018

Study Completion (Actual)

May 4, 2018

Study Registration Dates

First Submitted

January 3, 2020

First Submitted That Met QC Criteria

January 3, 2020

First Posted (Actual)

January 6, 2020

Study Record Updates

Last Update Posted (Actual)

January 6, 2020

Last Update Submitted That Met QC Criteria

January 3, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • SCH-2181

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Gene Expression Profiles in CML Non-responders

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe