Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing (ENABLE-NGS)

April 19, 2024 updated by: Royal Marsden NHS Foundation Trust

ENABLE-NGS: Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing

To enhance the diagnosis of unclassifiable, non-CLL B-LPDs using next-generation sequencing technology.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

In recent years, next generation sequencing has revealed the genomic landscape of lymphoid disorders and identified mutations that have improved our understanding of their pathogenesis. It has also revealed new targets for drug development. While some of these mutations, such as the BRAF V600E mutation in Hairy Cell Leukaemia (HCL)2, are now accepted as disease defining mutations, others such as MYD88 and NOTCH1/2 mutations are found in more than one subtype of B-LPD3. The overlapping nature of some of these molecular aberrations could have important implications for treatment of these disorders as we move towards targeted therapy. EZH2 inhibitors, which are currently in early phase trials, are one such example of targeted therapy for B-LPDs based on mutations identified by next generation sequencing (NGS)4. The genetic makeup of these tumours is also likely to influence future classification systems.

At present, an integrated approach incorporating morphology and immunophenotyping remains integral to the classification of B-LPDs. The Haemato-oncology department at the Royal Marsden Hospital has an international reputation in the development of immunophenotyping as a tool for the diagnosis of lymphoproliferative disorders. For example, the CLL score developed by the Haemato-Oncology department continues to be used in several centres around the world for the diagnosis of CLL5. A similar score proposed for HCL by our Haemato-Oncology department is also widely used (6). On a service evaluation, we found 100% concordance between a HCL score of 4 and presence of the BRAF mutation in samples referred to us (unpublished data).

Our plan therefore is to systematically study unclassifiable groups of B-LPD by creating a well-defined immunomorphology work flow for their identification. Samples thus identified will be screened using a next-generation sequencing (NGS) panel which is able to detect well established, B-LPD associated translocations and genetic mutations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
127

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United Kingdom
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients suffering with an unclassifiable B-cell lymphoproliferative disorder

Description

Inclusion Criteria:

  • Chronic, mature clonal B-cell malignancy that is not assignable to a specific WHO category by current technology (see flowchart in section below).

Exclusion Criteria:

  • Non-clonal B-cell proliferation.
  • High grade and/or immature clonal B-cell malignancy.
  • Bone marrow samples with less than 20% infiltration will be excluded
  • Samples from patients with a known classifiable chronic B-LPD based on lymph node biopsy for e.g. staging bone marrow samples on a patient with marginal zone lymphoma. If a definitive diagnosis is established on a subsequent lymph node biopsy, patient will remain on study and this will be correlated with NGS findings.
  • Patient unable to provide consent for tumour and germ line samples.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of cases where a definite category and/or detectable mutation can be identified.
Time Frame: 2 years
This will be reported as a percentage of the total number of cases sequenced
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Demographics and distribution in each immunomorphological category
Time Frame: 2 years
Age and sex distribution will be reported along with the proportion of cases in each immunomorphologic category
2 years
Correlation of each immunomorphological category with the mutation profile.
Time Frame: 2 years
The distribution of mutations within each immunomorphological category will be reported descriptively.
2 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Royal Marsden NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sunil Iyengar, Royal Marsden 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 17, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CCR4383

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.

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