Biology and Genetics of Smouldering Myeloma (COSMOS)
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|ClinicalTrials.gov Identifier: NCT05047107|
Recruitment Status : Recruiting
First Posted : September 16, 2021
Last Update Posted : September 16, 2021
|Condition or disease||Intervention/treatment|
|Smouldering Myeloma MGUS Multiple Myeloma||Other: No intervention|
MM is a cancer of plasma cells characterised by bone marrow infiltration by malignant plasma cells, kidney impairment, bone pain and elevated calcium levels1. There are approximately 5,500 new cases diagnosed annually in the UK, with a median survival of 5 years2. Significantly, despite improvements in conventional treatment options, MM remains incurable; patients inevitably relapse and will eventually die from their disease.3 MM is always preceded by defined precursor conditions, termed MGUS, and SMM. However, only 7% of MGUS patients and 50% of SMM patients progress to MM over a 5-year period4. In the UK, current practice favours commencing treatment only when there is evidence of end organ damage as the overall benefit of initiating early therapy is uncertain.
There is an increasing understanding that progression is determined by evolving changes in the tumour genome5 and changes in the immune microenvironment which support tumour growth, leading to progressively dysfunctional anti-tumour immunity. This project correlates changes in the tumour genome and immune microenvironment in individual patients with tumour progression and also aims to compare characteristics in patients with good and poor clinical outcomes with the objective of defining the drivers for disease progression. Furthermore, we aim to explore the use of blood samples to monitor tumour dynamics and immune function. Finally, we will also study the spatial distribution of immune cells and tumour cells in the bone marrow.
Clinical impact: A deeper understanding of the pathogenesis of MM will allow us to risk stratify patients with MGUS and SMM, and manage them accordingly as well as identifying subgroups of patients with MM who require different types of therapies, eg. more intensive multi-drug approaches for patients with adverse risk genetics.
|Study Type :||Observational|
|Estimated Enrollment :||500 participants|
|Official Title:||Characterising Risk and Biology Of Smouldering Myeloma for Early Detection Of Symptomatic Myeloma|
|Actual Study Start Date :||April 15, 2021|
|Estimated Primary Completion Date :||March 2025|
|Estimated Study Completion Date :||March 2025|
- Other: No intervention
- Genomic markers of progression [ Time Frame: 5 years ]To characterise genomic markers of progression by sequencing and studying the biology of bone marrow (BM) derived tumour cells.
- Immune biomarkers [ Time Frame: 5 years ]To define clonal heterogeneity and biomarkers of progression using liquid biopsies(blood), comparing with BM, and exploring the utility of serial samples.
Biospecimen Retention: Samples With DNA
BM aspirates and blood samples will be processed to extract tumour and non-tumour cells, as well as plasma and sera. Mononuclear cells (MNCs) will be prepared from these samples by centrifugal sedimentation, or red cell lysis, and plasma cells will be selected using immuno-magnetic beads coupled to monoclonal antibody specific to the plasma cell marker, CD138. In some cases, purified MM cells will be isolated by negative selection using RosetteSep method, which depletes immature progenitors, T-lymphocytes and NK cells. Immune cells, including CD4 and CD8 T cells will be separated by similar means for further assessment.
MM cells, immune cells and bulk MNCs will be frozen and stored for future DNA and RNA extraction. Cell lysates will be made for immuno-blotting and live cells will be frozen for use in functional assays.
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): NCT05047107
|Contact: Kwee Yong, Proffirstname.lastname@example.org|
|Contact: Louise Ainley, MDemail@example.com|
|University College London Hospitals||Recruiting|
|London, United Kingdom, NW1 2PG|
|Contact: Kwee Yong, Prof|
|Principal Investigator: Kwee Yong, prof|
|Sub-Investigator: Louise Ainley, MD|