Biology and Genetics of Smouldering Myeloma (COSMOS)

Characterising Risk and Biology Of Smouldering Myeloma for Early Detection Of Symptomatic Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; MGUS; Smouldering Myeloma
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Kwee Yong, Prof; Phone Number: 02076796233; Email: kwee.yong@ucl.ac.uk
• Study Contact Backup: Name: Louise Ainley, MD; Phone Number: 02076796233; Email: l.ainley@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals
    • Contact: Kwee Yong, Prof
    • Principal Investigator: Kwee Yong, prof
    • Sub-Investigator: Louise Ainley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic markers of progression	To characterise genomic markers of progression by sequencing and studying the biology of bone marrow (BM) derived tumour cells.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune biomarkers	To define clonal heterogeneity and biomarkers of progression using liquid biopsies(blood), comparing with BM, and exploring the utility of serial samples.	5 years

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Cancer Research UK

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2021
• Primary Completion (ANTICIPATED): March 1, 2025
• Study Completion (ANTICIPATED): March 1, 2025

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (ACTUAL): September 16, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma
• Other Study ID Numbers: 129657

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No