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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
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
University College, London

Study Description
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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.

Condition or disease Intervention/treatment
Smouldering Myeloma MGUS Multiple Myeloma Other: No intervention

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.

Study Design
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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Case-Only
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Groups and Cohorts
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Intervention Details:
  • Other: No intervention
    Non-interventional study

Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Any individual with a confirmed or suspected diagnosis of MGUS, SMM, or MM.
Criteria

Inclusion Criteria:

  • Any individual with a confirmed or suspected diagnosis of MGUS, SMM, or MM.

Exclusion Criteria:

  • Patients under the age of 18
  • Patients with active symptomatic myeloma at diagnosis
  • Patients with no evidence of MGUS, sMM or MM
  • Patients with rapidly rising paraprotein or serum free light chains suggestive of progressive disease at time of diagnosis or inclusion into study
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Kwee Yong, Prof 02076796233 kwee.yong@ucl.ac.uk
Contact: Louise Ainley, MD 02076796233 l.ainley@ucl.ac.uk

Locations
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United Kingdom
University College London Hospitals Recruiting
London, United Kingdom, NW1 2PG
Contact: Kwee Yong, Prof         
Principal Investigator: Kwee Yong, prof         
Sub-Investigator: Louise Ainley, MD         
Sponsors and Collaborators
University College, London
Cancer Research UK
More Information
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT05047107    
Other Study ID Numbers: 129657
First Posted: September 16, 2021    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
 Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Hypergammaglobulinemia