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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03344809
Recruitment Status : Unknown
Verified November 2017 by Royal Marsden NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : November 17, 2017
Last Update Posted : November 17, 2017
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Tracking Information
First Submitted Date February 7, 2017
First Posted Date November 17, 2017
Last Update Posted Date November 17, 2017
Study Start Date August 2016
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 13, 2017)
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
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: November 13, 2017)
  • 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
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing
Official Title ENABLE-NGS: Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing
Brief Summary 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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
  • 20mls of PB in EDTA
  • Further 20mls PB in EDTA in cases where the first sample does not yield adequate DNA.
  • 5ml of BM in EDTA (optional for patients not undergoing bone marrow as part of normal work-up.
Sampling Method Probability Sample
Study Population Patients suffering with an unclassifiable B-cell lymphoproliferative disorder
Condition Lymphoma
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: November 13, 2017)
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2020
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
Administrative Information
NCT Number NCT03344809
Other Study ID Numbers CCR4383
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Royal Marsden NHS Foundation Trust
Study Sponsor Royal Marsden NHS Foundation Trust
Collaborators Not Provided
Principal Investigator: Sunil Iyengar Royal Marsden NHS Foundation Trust
PRS Account Royal Marsden NHS Foundation Trust
Verification Date November 2017