Myeloma
Conditions
Keywords
multiplex, immunohistochemistry, hypoxia, single-cell RNA sequencing, pimonidazole, myeloma, microenvironment, metabolomics
Brief summary
The study is looking at how myeloma is related to low oxygen levels (hypoxia) in the bone marrow. This is to understand the disease better. It might also guide treatment in the future. For the study, we will run tests on a portion of the samples taken during a bone marrow biopsy. A bone marrow biopsy is taken as part of the diagnosis or follow up of myeloma. The tests in our study will look closely at the make-up of immune cells in the bone marrow, highlight areas of low oxygen, and look at genetic changes in cells from low-oxygen areas. We will ask patients to take a capsule the day before their bone marrow biopsy containing pimonidazole hydrochloride, a substance which will show up areas of low oxygen on tests. Overall we want to know: 1. If myeloma cells 'live' in areas of low oxygen in the bone marrow 2. What are the immune and bone marrow cells which are neighbours of myeloma cells? 3. Are there genetic changes in low oxygen myeloma cells For the pilot study, we want to know: 4. Can we use new techniques to study questions 1-3? The techniques we want to use are pimonidazole with multiplex immunohistochemistry and single cell RNA sequencing. The information we get from the tests will help us get a better understanding of how myeloma works. Future studies may also use these results to develop new kinds of drugs for myeloma.
Interventions
None listed
Sponsors
The Christie NHS Foundation Trust
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Male or female patients referred to The Christie NHS Foundation Trust from another hospital with proven multiple myeloma which may be either treatment naïve or previously treated. 2\. Aged 18 or over 3. World Health Organisation (WHO) performance status 0 to 2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks 4. Provision of written informed consent 5. Willing to undergo a bone marrow biopsy 6. Willing to take pimonidazole hydrochloride
Exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to staff at the study site) 2. Evidence of any significant clinical disorder or laboratory finding that made it undesirable for the patient to participate in the study 3. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative assessment of the utility of a set of investigational tools for investigating the bone marrow microenvironment in myeloma patients | Assessment is at the time of diagnosis. | Specifically we aim to determine the feasibility of using pimonidazole as a marker of hypoxia in conjunction with: A) Multiplex immunohistochemistry to characterise the spatial organization of cellular inflammatory elements and myeloma cells in the bone marrow, B)Single cell RNA sequencing to characterise the expression profile of myeloma cells in hypoxic areas of marrow |
Countries
United Kingdom
Contacts
Primary ContactAdam Jones, MBBS, MSc, MRCP
Outcome results
None listed