LymphomaENABLE-NGSNCT03344809
Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing
An observational study of Lymphoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
To enhance the diagnosis of unclassifiable, non-CLL B-LPDs using next-generation sequencing technology. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- How many people
- 127 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2016to May 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients suffering with an unclassifiable B-cell lymphoproliferative disorder
Who may be able to join
- Chronic, mature clonal B-cell malignancy that is not assignable to a specific WHO category by current technology (see flowchart in section below).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
Official title: 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.
Read the 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.
- Conditions
- Lymphoma
- Keywords
- lymphoma, unclassifiable, next, generation, sequencing
- Medical subject headings
- Lymphoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of cases where a definite category and/or detectable mutation can be identified.
This will be reported as a percentage of the total number of cases sequenced
Measured: 2 years
Secondary outcomes (2)
Demographics and distribution in each immunomorphological category
Age and sex distribution will be reported along with the proportion of cases in each immunomorphologic category
Measured: 2 years
Correlation of each immunomorphological category with the mutation profile.
The distribution of mutations within each immunomorphological category will be reported descriptively.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study startAug 2016
- Primary completionApr 2023
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sunil Iyengar, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03344809
- Sponsor's protocol ID
- CCR4383
- Acronym
- ENABLE-NGS
- Status last verified
- Apr 2024
- First submitted
- 7 Feb 2017
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ENABLE-NGS: Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing
- ClinicalTrials.gov ID
- NCT03344809
- Acronym / sponsor ID
- ENABLE-NGS / CCR4383
- Conditions
- Lymphoma
- Keywords
- lymphoma, unclassifiable, next, generation, sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Apr 2023 (actual)
- Study completion
- May 2026 (estimated)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To enhance the diagnosis of unclassifiable, non-CLL B-LPDs using next-generation sequencing technology.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients suffering with an unclassifiable B-cell lymphoproliferative disorder
Key inclusion criteria (1 listed)
- Chronic, mature clonal B-cell malignancy that is not assignable to a specific WHO category by current technology (see flowchart in section below).
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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 secondary outcomes
Demographics and distribution in each immunomorphological category
Time frame: 2 years
Correlation of each immunomorphological category with the mutation profile.
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sunil Iyengar principal investigator
Royal Marsden NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of cases where a definite category and/or detectable mutation can be identified. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.