Biology and Genetics of Smouldering Myeloma (COSMOS)
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| ClinicalTrials.gov Identifier: NCT05047107 |
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Recruitment Status :
Recruiting
First Posted : September 16, 2021
Last Update Posted : September 16, 2021
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| Tracking Information | |||||||||
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| First Submitted Date | September 15, 2021 | ||||||||
| First Posted Date | September 16, 2021 | ||||||||
| Last Update Posted Date | September 16, 2021 | ||||||||
| Actual Study Start Date | April 15, 2021 | ||||||||
| Estimated Primary Completion Date | March 2025 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures |
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.
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| Original Primary Outcome Measures | Same as current | ||||||||
| Change History | No Changes Posted | ||||||||
| Current Secondary Outcome Measures |
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.
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| 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 | Biology and Genetics of Smouldering Myeloma | ||||||||
| Official Title | Characterising Risk and Biology Of Smouldering Myeloma for Early Detection Of Symptomatic Myeloma | ||||||||
| Brief Summary | Observational clinical trial recruiting Smouldering Myeloma patients (SMM) or potential SMM patients. Study involves collecting blood and bone marrow samples to determine the features of the tumour genome and BM microenvironment, including immune dysfunction that are key drivers of progression from precursor conditions (MGUS and SMM) to MM. | ||||||||
| Detailed Description | 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. |
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| Study Type | Observational | ||||||||
| Study Design | Observational Model: Case-Only Time Perspective: Prospective |
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| Target Follow-Up Duration | Not Provided | ||||||||
| Biospecimen | Retention: Samples With DNA Description: 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. |
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| Sampling Method | Non-Probability Sample | ||||||||
| Study Population | Any individual with a confirmed or suspected diagnosis of MGUS, SMM, or MM. | ||||||||
| Condition |
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| Intervention | Other: No intervention
Non-interventional study
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| Study Groups/Cohorts | Not Provided | ||||||||
| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status | Recruiting | ||||||||
| Estimated Enrollment |
500 | ||||||||
| Original Estimated Enrollment | Same as current | ||||||||
| Estimated Study Completion Date | March 2025 | ||||||||
| Estimated Primary Completion Date | March 2025 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria | Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender |
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| Ages | 18 Years and older (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers | Not Provided | ||||||||
| Contacts |
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| Listed Location Countries | United Kingdom | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number | NCT05047107 | ||||||||
| Other Study ID Numbers | 129657 | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement |
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| Current Responsible Party | University College, London | ||||||||
| Original Responsible Party | Same as current | ||||||||
| Current Study Sponsor | University College, London | ||||||||
| Original Study Sponsor | Same as current | ||||||||
| Collaborators | Cancer Research UK | ||||||||
| Investigators | Not Provided | ||||||||
| PRS Account | University College, London | ||||||||
| Verification Date | September 2021 | ||||||||