Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing (ENABLE-NGS)
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|ClinicalTrials.gov 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
|Condition or disease|
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we found 100% concordance between a HCL score of 4 and presence of the BRAF mutation in samples referred to us (unpublished data).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|
|Estimated Enrollment :||120 participants|
|Official Title:||ENABLE-NGS: Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing|
|Study Start Date :||August 2016|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||July 2020|
- 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
- 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.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03344809
|Contact: Sunil Iyengar||020 8642 6011 ext firstname.lastname@example.org|
|The Royal Marsden NHS Foundation Trust||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Principal Investigator:||Sunil Iyengar||Royal Marsden NHS Foundation Trust|