Biology and Genetics of Smouldering Myeloma

NCT ID: NCT05047107

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2025-03-31

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.

Conditions

Smouldering Myeloma; MGUS; Multiple Myeloma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

No intervention

Non-interventional study

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University College London Hospitals

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Kwee Yong, Prof

Role: CONTACT

kwee.yong@ucl.ac.uk

02076796233

Louise Ainley, MD

Role: CONTACT

l.ainley@ucl.ac.uk

02076796233

Facility Contacts

Kwee Yong, Prof

Role: primary

Other Identifiers

129657

Identifier Type: -

Identifier Source: org_study_id