Biology and Genetics of Smouldering Myeloma

Multiple Myeloma Clinical Trial

— COSMOS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05047107
• Other study ID #: 129657
• Status: Recruiting
• Start date: April 15, 2021
• Est. completion date: March 2025

Study information

• Verified date: September 2021
• Source: University College, London
• Contact: Kwee Yong, Prof
• Phone: 02076796233
• Email: kwee.yong[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• MGUS
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma
• Smouldering Myeloma

Intervention

Other:
• No intervention
Non-interventional study

Locations

Country	Name	City	State
United Kingdom	University College London Hospitals	London

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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