The Development and Pilot Testing of a New Magnetic Resonance (MR) Imaging Protocol to Quantify Both Myeloma Disease Burden and Associated Bone Loss
Conditions: Myeloma, Monoclonal Gammopathy of Undetermined Significance (MGUS), Smouldering Myeloma
Sponsor: Oxford University Hospitals NHS Trust

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 myeLOma bOne MrI Study
The development and pilot testing of a new Magnetic Resonance (MR) imaging protocol to 
quantify both myeloma disease burden and associated bone loss 
Internal Reference Number / Short title: LOOMIS: myeLOma bOne MrI Study 
Ethics Ref: 18/SC/0046 
Date and Version No: v.4.0 21 May 2021 
Chief Investigator: 
Dr Karthik Ramasamy, Consultant Haematologist, Oxford University 
Hospitals NHS Foundation Trust, Cancer Centre, Churchill Hospital, Old 
Road, Headington, OX3 7LE 
Tel: 01865 235882 
Email: kramasamy@nhs.net  
Investigators:  
Dr Sarah Gooding, Research Fellow, Cancer Centre, Churchill Hospital, 
Old Road, Headington, OX3 7LE 
Email: sarah.gooding@ouh.nhs.uk  
Prof Chris Rodgers, Associate Professor of Biomedical Imaging, 
University of Oxford Centre for Clinical Magnetic Resonance Research, 
Level 0, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, 
Email: christopher.rodgers@cardiov.ox.ac.uk  
Dr M Kassim Javaid, Consultant in Metabolic Medicine, The Nuffield 
Department of Orthopaedics, Rheumatology and Musculoskeletal 
Sciences, Nuffield Orthopaedic Centre, Windmill Road, Headington, OX3 
7HE 
Email: kassim.javaid@ndorms.ox.ac.uk  
Sponsor:  
Oxford University Hospitals NHS Foundation Trust 
Joint Funders: 
Amgen Pharmaceuticals 
Oxford NIHR Biomedical Research Centre 
 
 
OOMIS 

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Chief Investigator Signature:  
 
No potential conflicts of interest. 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, host organisation, and members of the Research Ethics Committee, 
unless authorised to do so. 
 
 
 
 

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1. 
SYNOPSIS ..........................................................................................................................................5 
2. 
ABBREVIATIONS ................................................................................................................................6 
3. 
BACKGROUND AND RATIONALE ........................................................................................................8 
4. 
OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS ...................................................................... 10 
5. 
STUDY DESIGN ................................................................................................................................ 11 
6. 
PARTICIPANT IDENTIFICATION......................................................................................................... 12 
6.1. 
Study Participants .................................................................................................................... 12 
6.2. 
Inclusion Criteria ..................................................................................................................... 12 
6.3. 
Exclusion Criteria ..................................................................................................................... 12 
7. 
STUDY PROCEDURES ....................................................................................................................... 13 
7.1. 
Recruitment ............................................................................................................................ 13 
7.2. 
Informed Consent .................................................................................................................... 13 
7.3. 
Screening and Eligibility Assessment ........................................................................................ 14 
7.4. 
Study Assessments .................................................................................................................. 16 
7.5. 
Sample Handling...................................................................................................................... 17 
7.6. 
Discontinuation/Withdrawal from Study ................................................................................. 18 
7.7. 
Definition of End of Study ........................................................................................................ 18 
8. 
INTERVENTIONS (IF APPLICABLE) ..................................................................................................... 18 
9. 
SAFETY REPORTING ......................................................................................................................... 18 
9.1. 
Definition of Serious Adverse Events ....................................................................................... 19 
9.2. 
Reporting Procedures for Serious Adverse Events .................................................................... 19 
10. 
STATISTICS AND ANALYSIS ........................................................................................................... 19 
10.1. 
Description of Statistical Methods ....................................................................................... 19 
10.2. 
Analysis of Outcome Measures/Endpoints ........................................................................... 20 
11. 
DATA MANAGEMENT .................................................................................................................. 20 
11.1. 
Access to Data ..................................................................................................................... 20 
11.2. 
Data Recording and Record Keeping .................................................................................... 21 
12. 
QUALITY ASSURANCE PROCEDURES ............................................................................................ 21 
13. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................ 21 
13.1. 
Declaration of Helsinki ......................................................................................................... 21 
13.2. 
ICH Guidelines for Good Clinical Practice ............................................................................. 21 
13.3. 
Approvals ............................................................................................................................ 21 
13.4. 
Reporting............................................................................................................................. 21 
13.5. 
Participant Confidentiality ................................................................................................... 21 

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13.6. 
Expenses and Benefits ......................................................................................................... 22 
13.7. 
Other Ethical Considerations................................................................................................ 22 
14. 
FINANCE AND INSURANCE ........................................................................................................... 23 
14.1. 
Funding ............................................................................................................................... 23 
14.2. 
Insurance ............................................................................................................................. 23 
15. 
PUBLICATION POLICY .................................................................................................................. 23 
16. 
REFERENCES ................................................................................................................................ 25 
17. 
APPENDICES: ............................................................................................................................... 27 
17.1. 
APPENDIX A: Schedule of assessments ................................................................................. 27 
17.2. 
APPENDIX B: MRI SAFETY CHECKLIST ................................................................................... 27 

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1. SYNOPSIS 
Study Title 
The development and pilot testing of a new Magnetic Resonance (MR) imaging 
protocol to quantify both myeloma disease burden and associated bone loss 
Internal ref. no. / 
short title 
LOOMIS- myeLOma bOne MrI Study 
Study Design 
Observational Prospective Cohort  
Study Participants 
Group 1- Myeloma 
Group 2- Monoclonal Gammopathy of Uncertain Significance (MGUS) 
Group 3- Healthy Volunteers 
Planned Sample Size 
60  
Group 1- Myeloma- 34 
Group 2- MGUS - 13 
Group 3 - Healthy Volunteers - 13 
Planned Study Period 
September 2017 – December 2021 
 
Objectives 
Outcome Measures 
Primary 
 
To develop and pilot test a novel 
Magnetic Resonance (MR) imaging 
protocol with the aim to accurately: 
1. Quantify tumour burden  
2. Quantify bone loss  
 
Novel imaging based endpoints: 
1. DW-MRI (Diffusion Weighted- 
Magnetic Resonance Imaging): ADC 
(apparent diffusion coefficient) 
change (Pawlyn et al, 2016)  
2. Total spinal ‘hole’ volume 
3. Total spine ‘collapse’ volume 
4. FSA (Fine Structural Analysis): 
trabecular wall thickness (Rafferty 
et al, 2016) 
Correlate endpoints: 
 
Bone density (DXA imaging) 
 
Serum CTX-1 
 
Serum P1NP 
 
Further experimental serum 
biomarkers of myeloma 
bone disease 
Secondary 
 
To pilot test a novel MR imaging protocol 
with the aim to accurately: 
1. Detect longitudinal changes in 
tumour load with therapy 
2. Detect longitudinal changes in 
bone microarchitecture with 
therapy 
3. Assess participants Quality of 
Life (EQ-5D) throughout the 
study 
1 and 2 - Repeat quantification of 
endpoint parameters after induction 
therapy and best response achieved 
by IWMG criteria or at treatment 
failure 
 

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4. Assess participants experience of 
the novel MR imaging scan 
3 – Analyse participants quality of 
life using data from the EQ-5D-5L 
questionnaire 
 
4- Analyse participants experience 
of the novel MR imaging using data 
from MRI/DXA scanning 
questionnaire 
 
2. ABBREVIATIONS 
 
ADC 
Apparent Diffusion Coefficient 
CI 
Chief Investigator 
CRF 
Case Report Form 
DWI 
Diffusion Weighted Imaging 
DWMRI 
Diffusion Weighted Magnetic Resonance Imaging 
DXA 
Dual-energy X-ray Absorptiometry 
FSA 
Fine Structure Analysis 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonisation 
IMWG 
International Myeloma Working Group 
MGUS 
Monoclonal Gammopathy Of Uncertain Significance 
MR 
Magnetic Resonance 
MRI 
Magnetic Resonance Imaging 
NHS 
National Health Service 
NOC 
Nuffield Orthopaedic Centre 
NRES 
National Research Ethics Service 
PET-CT 
Positron Emission Tomography-Computed Tomography  
PI 
Principal Investigator 
PIL 
Participant/Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 

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SOP 
Standard Operating Procedure 
SRE 
Skeletal Related Events 
WBLDCT 
Whole-body low dose Computed Tomography 
sFLC 
Serum free light chains 
 
 

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3. BACKGROUND AND RATIONALE 
 
Multiple myeloma, a malignancy of monoclonal B-cells, is the second most common haematological 
malignancy, compromising of 2% of all cancers in the UK and is currently incurable.  At diagnosis and 
each relapse, treatment of myeloma consists of conventional chemotherapy combined with novel 
agents. In those fit enough, autologous (and in some cases allogeneic) stem cell transplantation is used 
to prolong remissions (NICE, 2016). A number of tests are used for disease quantification to guide 
therapy; however these tests each have limiting factors.  Bone marrow histology using a bone marrow 
biopsy is painful and invasive; it also cannot predict global myeloma infiltration, which is not uniform and 
varies through the skeleton, and no bone loss information can be obtained. Serum paraprotein, light or 
heavy chain quantification must be used for regular monitoring; however this fails in non-paraprotein 
secreting myelomas, and although it tracks the secretory capacity of a plasma cell clone, that feature can 
change over the course of the disease.   
PET-CT (positron emission tomography- computed tomography) is the imaging gold standard in myeloma 
for quantifying total disease burden (Cavo et al, 2017). This cannot however quantify bone loss, either 
microarchitecture changes or lytic lesions. It therefore cannot be used to track response to anti-bone-
resorptive therapies.  
There are a number of widely used modalities that are currently available to visualise bone destruction; 
including conventional MR (magnetic resonance), whole body low dose CT (WBLDCT) (Pianko et al, 2014) 
and X-ray skeletal survey. However, none of these techniques are quantitative (Marti-Bonmati et al, 
2015). Of particular note, high-resolution bone volume quantifying CT techniques cannot be used on the 
central skeleton due to high radiation exposure; although trialled on cortical bone in the peripheral 
skeleton (Farr et al, 2013), this is not the usual site of myeloma bone loss.  DXA (Dual-energy X-ray 
Absorptiometry) scans are widely used in the UK for assessing bone density in patients with osteoporosis 
but are an insensitive tool in myeloma as it does not show fractures (Marti-Bonmati et al, 2015), and 
therefore are not routinely commissioned for imaging myeloma patients.  All of these imaging modalities 
require significant time and resource commitment over a typical myeloma disease course. Typically a 
patient may require X rays, PET-CT and spinal MRI within a few weeks for complete staging. If there were 
a single imaging method that could provide all required quantified staging information this would have 
both economic and patient convenience benefits.  
The use of Magnetic Resonance Imaging (MRI) in Multiple Myeloma has increased dramatically over the 
last 10 years (Derlin & Bannas, 2014). MRI offers improved detection of lesions in the spine, pelvis, 
sternum, skull and scapulae as well as exceptional depiction of the spinal cord and nerve roots, detection 
of soft tissue manifestations and the ability to differentiate between physiological and myeloma-
infiltrated bone marrow. Several studies have shown that asymptomatic patients with detectable lesions 
on MRI have a higher probability to become symptomatic earlier than patients without such lesions.  This 
has therefore been incorporated in the revised IMWG diagnostic criteria (Rajkumar et al, 2014). 
In addition to morphological MRI, there are newer functional MR techniques such as diffusion-weighted 
imaging (DWI). However there is limited published data for DWI (Diffusion Weighted Imaging) in the 
context of initial staging. A recent study has shown that diffusion-weighted imaging not only allows for 
detection of myeloma manifestations such as lytic lesions (DW-MRI was found superior to the whole-
body x-ray for the detection of bone involvement in 20 patients with relapsed, refractory myeloma in all 

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areas of the skeleton except the skull), but also that the DWMRI-generated apparent diffusion coefficient 
(ADC) significantly differs before and after initiation of therapy, so allowing calculation of change in 
disease burden (Giles et al, 2015). DW-MRI uses ADC measurement to quantify disease and is influenced 
by tissue microarchitecture. The speed, quantitative capabilities and superior sensitivity compared with 
conventional MRI sequences have led to the adoption of DW-MRI at several leading myeloma centres 
worldwide. ADC measurements are not without challenges, as they can be influenced by scanner 
manufacturer and field strength, however are perceived to be less susceptible to equipment and 
physiological influences than PET-CT. In a recent trial (Pawlyn et al, 2016), DW-MRI scans were compared 
with FDG (f-fluorodeoxyglucose) PET-CT and found to detect a statistically significant higher burden of 
myeloma disease. Investigations into the patient experience of DW-MRI have suggested that the DW-MR 
imaging technique is acceptable to patients as 86% found the overall experience acceptable. It is 
therefore proposed to be a novel non-ionising radiation imaging modality for quantitative assessment of 
disease burden and therapy response (Latifoltojar et al, 2017; Pawlyn et al, 2016). Importantly however, 
DW MRI cannot measure bone density. 
The extent of lytic bone disease, the major cause of morbidity in myeloma affecting over 90% of patients, 
still cannot be quantified. Lytic lesions as seen on X-rays take many years to heal. In MGUS (Monoclonal 
gammopathy of uncertain significance); a precursor of multiple myeloma without any signs of the 
malignant disease (Bauerle et al, 2009); it is suspected that early bone destruction is associated with 
transformation to malignancy, but no appropriate imaging modality exists to assess or monitor this, 
meaning this patient cohort may be missing out on disease modifying therapies. We wish to address this 
important unmet clinical need by piloting a novel MR imaging assessment of disease burden and bone 
loss in myeloma. Farr et al using peripheral qCT have shown MGUS patients have early bone loss (Farr et 
al, 2013). This has been subsequently termed as monoclonal gammopthay of skeletal significance, 
MGSS (Drake, 2014). 
On to the state of the art DW-MRI technique of quantifying disease burden, we propose to add 2 further 
experimental MR components to quantify myeloma bone loss, which can take the form of a) lytic lesions 
(holes), b) vertebral collapse and c) trabecular thinning. We will address this in the following way: 
1. High resolution 3D imaging of spine and pelvis: ‘hole’ and ‘collapse’ volumes will be quantified. This is 
entirely novel and will be produced by OCMR scientists. 
2. Fine SA:  Osteotronix’ fineSA® (FSA) technology is able to extract microstructural information from MRI 
data sets acquired on a standard clinical MRI scanner. In this study, we are particularly interested in 
using the FineSA metric as a correlate of trabecular wall thickness, to indicate bone remodelling. The FSA 
metric has been shown to correlate tightly with gold standard bone density measurements in rats (Evans 
et al, 2014) and human cadaveric spine specimens (Rafferty et al, 2016). The only other means to 
measure these parameters is by computed tomography, not feasible in the human body in vivo due to 
the high radiation dose that would result from microstructural CT of central bones. FSA will be 
performed at two sites in the lumbar spine, and repeated on each patient (within the same 
appointment) to assess reproducibility. Further central skeleton sites may be added with technique 
development. 
We therefore aim to develop and pilot a MR imaging protocol and assess its ability to achieve the 
following: quantification of tumour burden and bone loss, detecting longitudinal changes in tumour load 

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with therapy and detecting longitudinal changes in microarchitecture with therapy. We also aim to 
investigate sensitivity of the different imaging techniques in detection of bone loss. This will be 
investigated by correlating the DXA imaging data (accepted imaging for measuring longitudinal changes 
in bone density) with our experimental protocol, to see if it is possible to achieve quantifiable data of 
bone density.   
 
We hypothesize that this imaging tool will be superior to the combined current standard-of-care 
investigations in the quantification of tumour burden and bone loss. There are currently no tools 
available for quantifying structural changes to bone and overall bone loss in myeloma.  
To our knowledge, this has never been done before; if shown to be feasible, such a method would have 
two important applications: to precisely guide commissioned therapies in the clinic, so improving patient 
management; and as an exciting, novel research tool for the longitudinal combined assessment of 
tumour burden and cancer‐induced bone disease in response to therapy. 
 
4. OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS 
 
 
Objectives 
Outcome Measures  
Primary 
To develop and pilot test a novel MR 
imaging protocol with the aim to 
accurately: 
1. Quantify tumour burden  
2. Quantify bone loss  
 
Novel imaging based endpoints: 
1. DW-MRI: ADC change (Pawlyn 
et al, 2016)  
2. Total spinal ‘hole’ volume 
3. Total spine ‘collapse’ volume 
4. FSA: trabecular wall 
thickness (Rafferty et al, 2016) 
Correlate endpoints: 
 
Bone density (DXA 
imaging) 
 
Serum CTX-1 
 
Serum P1NP 
 
Further experimental 
serum biomarkers of 
myeloma bone disease 
 
Secondary 
To pilot test a novel MR imaging 
protocol with the aim to accurately: 
1. Detect longitudinal 
changes in tumour load with 
therapy 
2. Detect longitudinal 
changes in bone 
 
1 and 2 - Repeat quantification of 
endpoint parameters after 
induction therapy and best 
response achieved by IWMG 
criteria or at treatment failure 
 

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microarchitecture with 
therapy 
3. Assess participants 
Quality of Life (EQ-5D) 
throughout the study 
 
4. Assess participants 
experience of the novel MR 
imaging scan 
3 – Analyse participants quality of 
life using data from the EQ-5D-5L 
questionnaire 
 
4- Analyse participants experience 
of the novel MR imaging using 
data from MRI/DXA scanning 
questionnaire 
 
5. STUDY DESIGN 
 
This novel MR protocol is developing new metrics and combining elements that have not previously been 
combined therefore, there will be a protocol development phase prior to trial recruitment in which a group 
of healthy volunteers will be scanned to ensure timings and data collection is optimized. This phase will 
take place prior to trial start and is not included as part of this protocol, as it is already covered by REC 
approval for OCMR protocol development. 
Once the protocol development phase has been completed, 60 subjects will be recruited to take part in 
this study; Group 1: Myeloma, (n=34), Group 2: MGUS, (n=13) and Group 3: Healthy age-matched 
volunteers, (n=13). Participants from Groups 1 and 2 will be identified and approached by a healthcare 
professional in the oncology clinic at the Churchill Hospital, Oxford. Group 3 participants will usually be 
the partners of the participants from group 1 and 2, and they will be recruited alongside the participants 
in Groups 1 and 2.   
As participants in Groups 1 and 2 will be recruited at the point of either diagnosis or relapse, any standard 
investigations their clinician deems necessary for their diagnostic evaluation within NHS protocols will also 
be performed. Following recruitment, all participants (Groups 1-3) will undergo the first study 
appointment, the experimental combined MR imaging protocol. Alongside this, participants in Groups 1 
and 2 only will undergo the DXA imaging scan and the bone biomarker blood and urine tests. Once both 
imaging appointments have been completed, all participants will be asked to complete a short 
questionnaire relating to the MRI imaging and Groups 1 and 2 will be asked to complete this questionnaire 
for the DXA imaging too; no questionnaires are to be completed for the bone biomarker test. Groups 1 
and 2 participants will also be asked to complete a validated quality of life questionnaire.  
Participants in Groups 1 and 2 will undergo a further experimental MR scan, DXA imaging and bone 
biomarker blood tests at 6 months or at time of progression/relapse, whichever is sooner (but no sooner 
than 3 months after the initial investigations) to evaluate change in disease burden and bone loss. The 
reason participants in Group 2 will be rescanned at 6 months even if they have not progressed to myeloma 
and are not on therapy, is to address the following questions, 1. Can trabecular thinning progression be 
detected with time in MGUS patients whose paraprotein is stable or rising? 2. Reproducibility test: In 

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patients with a stable paraprotein, if assumed that trabecular thickness is stable or at most slightly worse 
over 6 months, is trabecular quantification reproducible over time? 
In addition to this, all participants in Groups 1 and 2 will also be asked to complete the short questionnaire 
relating to the MRI and DXA imaging and the quality of life questionnaire for assessment of patient 
experiences of both imaging procedures, both at the first study appointment and at the 6 month follow 
up appointment. Standard of care clinical investigations will be repeated within NHS protocols if clinically 
indicated. Results of relevant NHS diagnostic investigations, clinical outcomes and survival data will be 
collected and stored. 
 
6. PARTICIPANT IDENTIFICATION 
6.1. Study Participants 
 
Patients with newly diagnosed or relapsed myeloma, smouldering myeloma (Group 1; n=34), MGUS 
(intermediate or high risk) (Group 2; n= 13), and healthy age-matched volunteers (Group 3; n=13) are 
eligible to be included in the trial if they meet the following criteria: 
6.2. Inclusion Criteria  
 
Inclusion Criteria (All Groups) 
 
Participant is able to and willing give informed consent for participation in the study. 
 
Male or Female, aged 18 years or above. 
Inclusion Criteria (Groups 1 and 2) 
 
Newly diagnosed myeloma or newly- relapsed myeloma eligible for next therapy,  
 
Smouldering myeloma or intermediate or high risk MGUS 
 
Patients attending Oxford NHS Haematology-oncology centre  
 
Diagnoses of MGUS, Smouldering Myeloma and MM- made in accordance with the clinical diagnostic 
criteria set forth by IMWG (International Myeloma Working Group)  
 
6.3. Exclusion Criteria  
 
Exclusion Criteria (All Groups) 
 
Those who are unable or unwilling to give informed consent 

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 
Women who may be pregnant, breast feeding or women of child-bearing potential who are unwilling 
or unable to take sufficient precautionary measures will be excluded due to DXA imaging. 
 
Exclusion Criteria (Groups 1 and 2) 
 
Signs of Spinal Cord Compression 
 
Patients with documented metastatic lesions from another type of malignancy 
 
Known contraindication for a MRI scan (see Appendix B: contraindications to MR scan), including 
unacceptable pain on lying flat for 1 hour.  
 
7. STUDY PROCEDURES 
Summary: In order to pilot test a novel MRI imaging protocol, this study will compare current, NHS-
available myeloma tumour and bone disease assessment tools, with the novel MR imaging technique. 
Blood sampling for bone turnover biomarkers, DXA imaging and the novel MR scan will be performed in 
addition to any standard NHS tests deemed necessary by clinical care team. Three groups of participants 
will be included, Group 1 (Myeloma), Group 2 (MGUS) and Group 3 (Healthy Volunteers). Group 3 will 
only receive a single MR scan with no further investigations whereas Groups 1 and 2 will go onto receive 
DXA scan and blood tests. Relevant baseline information including medical history, prior course of 
disease and use of bone modifying therapy will be recorded at start of study for Groups 1 and 2, and 
once more at 6 months post-recruitment, or at relapse/progression if sooner.  
7.1. Recruitment 
Newly diagnosed or newly relapsed myeloma patients (Group 1) with or without X-ray detectable bone 
disease, Smouldering myeloma and high or intermediate MGUS patients (Group 2), without X-ray 
detectable bone disease, will be invited to participate. Healthy age-matched volunteers (Group 3) will be 
recruited from the local myeloma support group community, (for example patients’ partners).  
Patients will be identified by the clinician or clinical care team. Potential patients will then be 
approached by the myeloma clinical research team during a routine clinic visit and given information 
about the study. If the participant is interested then they will have a further detailed discussion about 
the study with a research coordinator and will be given the participant information sheet to take home. 
They will return to clinic after a minimum period of 24 hours, and will have the opportunity to ask any 
questions regarding the study. If the participant remains happy to enter the study, their informed 
consent will be obtained by the investigator prior to initiating any study related investigations. 
We anticipate a 10% screen failure for group 1 participants, primarily due to pain and contraindications 
for MRI. We anticipate 5% screen failure rate for group 2 participants due to contraindications for MRI 
scan. Both of these figures have been incorporated in the sample size calculations.  
7.2. Informed Consent 

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Informed consent will be taken at a routine clinic visit. The participant must personally sign and date the 
latest approved version of the Informed Consent form before any study specific procedures are 
performed. 
Copies of the Participant Information Sheet and Informed Consent will be presented to the participants 
detailing no less than: the exact nature of the study; what it will involve for the participant; the 
implications and constraints of the protocol; the known side effects and any risks involved in taking part. 
It will be clearly stated that the participant is free to withdraw from the study at any time for any reason 
without prejudice to future care, without affecting their legal rights, and with no obligation to give the 
reason for withdrawal. A member of the clinical team will talk through the PIS with the participant 
before Informed Consent is obtained. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will 
participate in the study. Written Informed Consent will then be obtained by means of participant dated 
signature and dated signature of the person who presented and obtained the Informed Consent. The 
person who obtained the consent must be suitably qualified and experienced, and have been authorised 
to do so by the Chief Investigator. A copy of the signed Informed Consent will be given to the participant. 
The original signed form will be retained at the study site. 
Those who have not communicated a decision regarding consent may be re-approached on one occasion 
after 2 months by the local research team. 
 
 
7.3. Screening and Eligibility Assessment 
 
7.3.1 Screening Logs 
The research team will be expected to maintain a screening log of all potential participants. Participants 
will not be registered at consent and therefore during screening, potential participants should be 
identified by limited information only; this should include initials, date of birth, screening date and 
outcome of the screening process (e.g. enrolled into study, reason for ineligibility if known, or refused to 
participate). Screening logs will be filed in the trial master file.   
7.3.2 Screening Assessments 
All screening study assessments must be completed before any study procedures are carried out. 
 
The following assessments will be carried out in order to establish eligibility for the study for participants 
in Groups 1 and 2 only. 
 
Medical History 

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Detailed history of myeloma/MGUS including; date of diagnosis, staging (International Staging 
System) and location(s) of bone disease as per standard of care should be recorded. Detailed 
description of all prior and ongoing diseases and disorders should be documented along with any 
myeloma or bone strengthening therapies that were received. 
 
Particular Details on history of fractures, history of osteoporosis, bone pain and analgesia 
requirements should be documented. Details on use of radiotherapy or vertebral augmentation 
should be collected. 
 
 
Treatment History and Concomitant Medication(s) 
Details of treatment history and current concomitant medication including all medications, 
treatments and therapies used in the prior 4 weeks, as well as those currently being taken should be 
recorded. 
 
 
Physical Examination 
Physical examination including assessment of ECOG status (Group 1 only), height and weight should 
be recorded for all participants. 
 
 
Local Clinical Laboratory Evaluations  
- 
Biochemistry: Sodium, Potassium, Total Protein, Albumin, Adjusted Calcium, Bicarbonate, 
Magnesium, Phosphate, Urea, Creatinine, LFTs, CRP, LDH, Uric acid, Glucose, Creatinine 
Clearance 
- 
Immunology: Beta-2 microglobulin, paraprotein, quantitative immunoglobulins, serum free 
light chains 
- 
Haematology: haemoglobin, haematocrit, bilirubin, WBC, platelet count, neutrophils, 
lymphocytes  
- 
Bone marrow assessment (only Myeloma and Smouldering myeloma): bone marrow aspirate 
and trephine to confirm diagnosis of myeloma 
- 
Urine pregnancy test: for women of child bearing potential (WCP)     
Participants in Group 3 will undergo the following screening assessments before any study procedures 
are carried out: 
 
Medical History 
Detailed history of any relevant previous medical conditions and their treatments  
 
Physical Examination  
Physical examination of height and weight to be recorded 
7.3.3 Recruitment Logs 
Participants deemed eligible after screening will be registered on to the study and be given a unique 
Study ID. Registered participants will be recorded on an enrolment log with information including Study 
ID, Date of Birth, Initials and hospital number as well as date of consent. No personal information, which 
may identify the participant, should be included on the recruitment log. 
7.3.4 Participant Trial Card 

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After a participant has been enrolled onto the study, the research staff should inform the participant of 
their Study ID and provide a completed Participant Trial Card including details of dates of the scans and 
staff contact details. 
 
7.4. Baseline Assessments 
7. 4.1 Baseline Assessments for Groups 1 and Group 2  
Once consent has been given, the first study appointment will be offered, within four weeks. This first 
study visit will include the MR imaging protocol, DXA scanning, bone biomarker blood/urine tests and 
completion of both questionnaires. These procedures are described in further detail below. An 
administrator will manage these attendance arrangements; however, participants will be required to 
make arrangements for transportation to and from the OCMR and NOC. Participants will be given the 
opportunity to claim back the travel expenses and details of how to do this is available in the Participant 
Information Sheet. Whenever possible, the administrator will try and arrange for the MRI and DXA scan 
to happen on the same day, should this not be possible and the scans are arranged for different days, the 
participants will have to attend an additional study visit.  
1. Blood and urine samples for bone turnover biomarkers total ALP, PINP and serum 
CTX1 (Vasikaran et al, 2011). This will require a morning fasted 20ml clotted (serum) blood 
sample to be taken. Additional experimental assays of biomarkers for myeloma bone disease will 
be performed on these samples at the Oxford University Hospitals NHS Foundation trust 
laboratory. This assessment will take approximately 10 minutes. 
2. Body composition using whole body DXA (1 hour radiology appointment at the NOC (Nuffield 
Orthopaedic Centre)). Bone Mineral Density (BMD) will be measured by (DXA) using a study 
approved densitometer. BMD measurements will be made at the lumbar spine (L1-4), hip, whole 
body and an Instant Vertebral Assessment (IVA). If participants have already had a DXA scan at 
one of these sites within 2 months of the visit date, then that scan will be used and the scan will 
not be repeated for that site. This assessment will take approximately 50 minutes. 
3. Experimental MR imaging protocol (1 hour radiology appointment). MRI scans will be performed 
in a 60-minute protocol on the 1.5T or 3T Avanto MRI scanner (Siemens, Germany) installed at 
OCMR (Oxford Centre for Magnetic Resonance), John Radcliffe Hospital, Headington, Oxford, 
OX3 9DU. Scans will include: localizer images, high-resolution 3D imaging of the pelvis and 
lumbar spine, diffusion-weighted MRI imaging following the method described for use in 
myeloma patients by Giles et al  (Giles et al, 2015; Giles et al, 2014; Pawlyn et al, 2016), and an 
experimental bone density quantification MR method based on published techniques (Evans et 
al, 2014; Rafferty et al, 2016), using software from Osteotronix Ltd, in the pelvis and two sites in 
the lumbar spine. Blinded data gathered from experimental MRs will be used to generate disease 
burden in percentage marrow infiltration, high-resolution 3D imaging-generated total spinal lytic 
and collapse volumes, and bone structure quantification. Marrow infiltration will be correlated 
with marrow infiltration data as determined by bone marrow biopsy (and PET-CT scans where 
performed). MR-generated bone density quantification and total spinal lytic and collapse 
volumes will be correlated with bone mineral density as estimated by DXA scan. As there is no 

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accepted “gold standard” method for quantifying myeloma-associated bone loss against which 
to compare, in all the healthy volunteers and in 10 myeloma patients who are tolerating the 
procedure without problem and who are willing repeat MR bone density measurements will be 
performed (a subsection of the whole protocol, lasting max. 15 minutes) within each attendance, 
to assess reproducibility.  
4. At the end of both the experimental MR and the DXA scan, all participants will be asked to 
complete the Quality of Life Questionnaire and the novel MR experience questionnaire. This 
assessment will take approximately 15 minutes. 
See Appendix A for time frame of assessments. 
No contrast medium will be used.  
7.4.2 Baseline Assessments for Group 3 (Healthy Volunteer) 
All baseline assessments for Group 3 will be the same as those for Groups 1 and 2 with the exception of 
Number 1 and 2. Healthy volunteers will not be required to give any (blood/urine) samples or have the 
DXA imaging.  
If the MRI and DXA scans are on the same day for Groups 1 and 2, then the baseline visit will last for 
approximately 2.5 to 3 hours. However, if the MRI and DXA scans are on different days, then the baseline 
visit will last for approximately 1.5 to 2 hours and the DXA scan for approximately 1 hour. The baseline 
visit for Group 3 will last approximately 1.5 to 2 hours. 
7.5. Subsequent Visits 
For Groups 1 and 2, a follow up visit will take place 6 months after the baseline assessment. 
Tests 1, 2, 3 and 4 from baseline assessment will be repeated in exactly the same way for both Group 1 
and 2. 
Repeat data collection (on intervening treatment and disease monitoring results, from hospital records) 
will be performed. 
No subsequent data collection or assessment will be performed on Group 3 (Healthy volunteers) at 6 
months, as the only purpose of their inclusion is to establish reproducibility and a normal range for 
experimental MR output data. Therefore, group 3 participation stops at the end of their baseline 
assessments. 
 
7.6. Sample Handling 
All participants will be assigned a unique study ID which will also be used to identify samples. All 
laboratory samples, will be anonymised to the research team for this study however, direct clinical care 
team will have access to identifiable information in order to create a report for clinical purposes to 
inform participants care. 

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Blood and urine samples for bone turnover biomarkers total ALP, PINP and serum CTX1 will be taken at 
baseline and follow up at 6 months for Groups 1 and 2; no samples will be obtained from participants in 
Group 3. This will require a morning fasted 20ml clotted (serum) blood sample to be taken. Additional 
experimental assays of biomarkers for myeloma bone disease will be performed on these samples at the 
Oxford University Hospitals NHS Foundation trust laboratory. All samples collected from Groups 1 and 2 
at both baseline and follow up will be stored for the duration of the study to run analytes in parallel to 
limit batch wise processing. Samples collected for this study will not be stored for use in other research 
and will be destroyed after analysis. These samples will only be accessible to study staff and authorised 
personnel.  
 
7.7. Discontinuation/Withdrawal from Study 
Each participant has the right to withdraw from the study at any time.  In addition, the Investigator may 
discontinue a participant from the study at any time if the Investigator considers it necessary for any 
reason including: 
 
Pregnancy 
 
Ineligibility (either arising during the study or retrospectively having been overlooked at screening) 
 
Significant protocol deviation 
 
Significant non-compliance with treatment regimen or study requirements 
 
Withdrawal of Consent 
 
Loss to follow up 
For participants who are withdrawn from the study, identifiable data or tissue already collected with 
valid consent would be retained and used in the study. No further data or tissue would be collected or 
any other research procedures carried out on or in relation to the participant. All withdrawal information 
including reason for withdrawal will be recorded on the Withdrawal CRF.  
Every effort will be made to replace participants who have been withdrawn from the study. 
7.8. Definition of End of Study 
 
 
The ending of the study is the date of the final MR imaging assessment of the last participant.  
8. INTERVENTIONS (IF APPLICABLE) 
8.1 DW-MR imaging scans 
MRI scans will be performed in a 60-minute protocol on the 1.5T Avanto MRI scanner (Siemens, 
Germany) installed at OCMR. Scans will include: localizer images, high-resolution 3D imaging of the pelvis 
and lumbar spine, diffusion-weighted MRI imaging following the method described for use in myeloma 
patients by Giles et al  (Giles et al, 2015; Giles et al, 2014; Pawlyn et al, 2016), and an experimental bone 
density quantification MR method based on published techniques (Evans et al, 2014; Rafferty et al, 
2016), using software from Osteotronix Ltd, in the pelvis and two sites in the lumbar spine. 

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8.2 DXA scans 
DXA scans will be performed in a 1 hour protocol on the DXA scanner installed at the NOC. Scans will 
include: body composition, bone mineral density measured at the Lumbar spine (L1-4), hip, whole body 
and Instant Vertebral Assessment. 
9. SAFETY REPORTING 
9.1. Definition of Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that: 
 
results in death 
 
is life-threatening 
 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
 
results in persistent or significant disability/incapacity 
 
consists of a congenital anomaly or birth defect. 
 
Other ‘important medical events’ may also be considered serious if they jeopardise the participant or 
require an intervention to prevent one of the above consequences. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event that hypothetically 
might have caused death if it were more severe. 
9.2. Reporting Procedures for Serious Adverse Events 
 
A serious adverse event (SAE) occurring to a participant should be reported to the REC that gave a 
favourable opinion of the study where in the opinion of the Chief Investigator the event was ‘related’ 
(resulted from administration of any of the research procedures) and ‘unexpected’ in relation to those 
procedures. Reports of related and unexpected SAEs should be submitted within 15 working days of the 
Chief Investigator becoming aware of the event, using the NRES report of serious adverse event form 
(see IRAS/NRES/HRA website). 
10. STATISTICS AND ANALYSIS 
10.1. 
Description of Statistical Methods 
 

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The primary outcome of this study is the ADC in patients with and without a complete/very good partial 
response to therapy at follow-up. It is estimated that for group 1, between baseline and follow-up, 85% of 
individuals will reduce their myeloma burden from 40% to 10% or less compared with 15% who will achieve 
a partial response (a ratio of 0.15).  
 
A previous study in a similar population the median ADC score improved from 0.79 (IQR 0.66 to 1.26) to 
1.5 (IQR 0.88 to 1.83) in those with a complete/very good partial response compared with 0.66 (IQR 0.52 
to 0.87) to 0.75 (0.51 to 1.27) in those with a partial response [Latifoltojar BJH 2016].  
 
To detect a similar difference in this cohort with an ADC in complete/ very good partial response of 1.5 at 
follow-up vs. 0.75 in those with a partial response, a conservative estimated SD of 0.5, and a ratio of 0.15 
will require 34 individuals in total (29 vs. 5) with 80% power and 0.05 type I error. We will, therefore, aim 
to recruit a total of 37 (31 vs. 6) participants for the study to allow for a dropout rate of 5%.  
10.2. 
Analysis of Outcome Measures/Endpoints 
 
Differences in baseline characteristics between participants groups (1, 2 and 3) will be compared using chi-
square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. 
 
To assess ability of MRI to detect improvement or deterioration in tumour burden and bone health, 
differences between DW-MRI data imaging from the two time-points (baseline and 6 months follow up) 
will be tested using paired t test. In addition, ADC, total spine ‘hole’ and ‘collapse’ volume and FSA 
trabecular wall thickness will be compared with bone mineral density at the lumbar spine, total hip and 
femoral neck T score and g/cm2, serum CTX-1 and PINP using correlation analysis in group 1 (complete/very 
good partial response vs. partial response) and in group 2. These models will be run at baseline and at 
follow-up.  
 
Differences between groups 1 and 2 in experimental MR measurements at follow up will be estimated 
using one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA) when baseline values 
and potential confounders (including gender, age and body mass index (BMI)) are adjusted. Endpoints will 
be checked for normality and transformed if possible.  
 
In order to determine the change in EQ-5D throughout the study, repeated measured linear regression 
analysis will be used where EQ-5D at baseline and follow up will be included as outcome and group as 
exposure. 
 
Finally, a descriptive analysis of the novel MR imaging scan questionnaire will be conducted to understand 
participant’s experience with the new technique. 
 
11. DATA MANAGEMENT 

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11.1. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor or host institution for 
monitoring and/or audit of the study to ensure compliance with regulations.  
Only authorised personnel involved in the clinical care of the patient will be able to access medical 
records and personal information for the purposes of the study or to inform clinical care.   For 
confidentiality purposes, all participant information outside of clinical use will be anonymised with 
unique Study ID used to identify the patient. The research data will be stored and backed up using data 
protection structures within the Oxford University Hospitals NHS Foundation Trust (Sponsor) and 
University of Oxford. External collaborators will only be able to access anonymised patient data.  
 
We will use password protection, ensuring computers cannot be accessed by people outside of the 
research unit, separating patient identifiers from clinical/research data and restricting access to who is 
able to link these two sets of data to the investigators on the study team. Electronic transfer of 
anonymised data will only use encrypted data. 
11.2. 
Data Recording and Record Keeping 
All essential documentation (CRFs) and research records will be stored in the Haematology Department 
administration offices, Churchill Hospital of Oxford University Hospitals NHS FT, in accordance with the 
applicable regulatory requirements with access to stored information restricted to authorized personnel 
only. All questionnaire and source document data will be entered on to a study database at the Oxford 
site. All electronic documentation and information will be kept on secured servers and computers in 
secured office areas. All documents will be version controlled. Essential documents will be archived as 
soon as practicable after the last patient entered onto the study has had their last study visit. All archived 
documents will be stored for 5 years in a secure location, and remain under access control of the CI, 
sponsor and regulatory authorities with an audit trail when material is retrieved. 
12. QUALITY ASSURANCE PROCEDURES 
The study may be monitored, or audited in accordance with the current approved protocol, ICH GCP, 
relevant regulations and standard operating procedures. 
13. ETHICAL AND REGULATORY CONSIDERATIONS 
13.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki.  
13.2. 
ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant regulations and 
with the Good Clinical Practice. 

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13.3. 
Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising 
material will be submitted to an appropriate Research Ethics Committee (REC), and host institution(s) for 
written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
13.4. 
Reporting 
The CI shall submit once a year throughout the study or on request, an Annual Progress report to the REC 
Committee, host organisation and Sponsor.  In addition, an End of Study notification and final report will 
be submitted to the same parties. 
13.5. 
Participant Confidentiality 
The study will be run according to ICH GCP after review by the relevant ethics committee. The study staff 
will ensure that the participants’ anonymity is maintained.  The participants will be identified only by a 
participant ID on all study documents and electronic database, with the exception of the CRFs where 
initials and DOB may be added. Documents with participant’s identifiable information on will be filed and 
stored securely in locked filing cabinets in the Late Phase Haematology Department, Churchill Hospital; 
these will only be accessible to authorised personnel. All documents will be stored securely and only 
accessible by study staff and authorised personnel. The study will comply with the Data Protection Act 
which requires data to be anonymised as soon as it is practical to do so.  
13.6. 
Expenses and Benefits 
 
All participants will be entitled to claim up to a maximum amount of £40 for travel expenses at the end 
of their participation in the trial. They will be required to fill out the travel expense form and hand this in 
along with the receipt to study staff. Once the claim has been processed, the payment will be made to 
the participants’ account via the trust finance office. 
13.7. 
Other Ethical Considerations 
Any clinically significant incidental findings during testing of blood samples or during the scanning 
procedures (both MRI and DXA) will be reported to the CI and the CI will then report these to the patient 
and GP.  
 
DXA: 
DXA imaging entails a small exposure to radiation, equivalent of up to 21 days of background radiation 
for the duration of the study. The results of the lumbar spine, hip and vertebral fracture assessment will 
be made available to the patient’s cancer care team for further clinical management. The Whole body 

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DXA will not routinely be reported on. Any incidental findings will be reported to the CI and the CI will 
then report these to the patient and GP. 
MRI scan: 
MRI safety checklist review will be conducted before admission into the scanner. Scan will last up to 60 
minutes. Patients will be given sufficient non-sedating pain relief prior to the scan if required, and 
positioning will be optimised according to any potential chronic bone pain. If a patient finds lying in the 
scanner too uncomfortable despite pain relief, the procedure will be abandoned. MRI is safe and non-
invasive and does not involve any ionising radiation (x-rays). No contrast injections will be given during 
the scan. 
Blood sample collection: 
Patient’s skin will be prepped with an anti-septic wipe, which very rarely can cause a skin reaction. If a 
patient knows they are allergic to the anti-septic prep, another sterile agent will be used. They will then 
feel a sharp scratch as the needle is inserted and blood is drawn up into the sample bottles. It is 
exceedingly rare for blood tests to be complicated; however bleeding and infection are potential risks 
that will be minimised as much as possible by monitoring for bleeding after the test, and using sterile 
equipment and the sterile non-touch technique. All procedures will be carried out by appropriately 
trained healthcare professionals.  
 
14. FINANCE AND INSURANCE 
14.1. 
Funding 
This study is partly funded by: Oxford NIHR Biomedical Research Centre. Amgen provides funding 
towards biomarkers, DXA and research MR scans. 
14.2. 
Insurance 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you are harmed 
whilst taking part in a clinical research study as a result of negligence on the part of a member of the 
study team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University Hospitals NHS 
Foundation Trust, therefore, cannot agree in advance to pay compensation in these circumstances. 
In exceptional circumstances an ex-gratia payment may be offered. 
 
15. PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and 
any other publications arising from the study. Authors will acknowledge that the study was funded by 

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the Oxford NIHR Biomedical Research Centre and Amgen. Authorship will be determined in accordance 
with the ICMJE guidelines and other contributors will be acknowledged. 
 
 

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16. REFERENCES 
1.Bauerle, T, Hillengass, J, Fechtner, K, Zechmann, CM, Grenacher, L, Moehler, TM et al (2009) Multiple 
myeloma and monoclonal gammopathy of undetermined significance: importance of whole-body versus 
spinal MR imaging. Radiology, 252, 477-485. 
 
2.Cavo, M, Terpos, E, Nanni, C, Moreau, P, Lentzsch, S, Zweegman, S et al (2017) Role of <sup>18</sup>F-
FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a 
consensus statement by the International Myeloma Working Group. The Lancet Oncology, 18, e206-e217. 
 
3.Derlin, T, Bannas, P (2014) Imaging of multiple myeloma: Current concepts. World J Orthop, 5, 272-282. 
 
4.Drake, MT (2014) unveiling skeletal fragility in patients diagnosed with MGUS: no longer a condition of 
undetermined significance? J Bone Miner Res, 29, 2529-2533. 
 
5.Evans, BAJ, James, TW, James, K, Cox, A, Farr, L, Paisey, SJ et al (2014) Preclinical Assessment of a New 
Magnetic Resonance-based Technique for Determining Bone Quality by Characterization of Trabecular 
Microarchitecture. Calcified Tissue International, 95, 506-520. 
 
6.Farr, JN, Zhang, W, Kumar, SK, Jacques, RM, Ng, AC, McCready, LK et al (2013) Altered cortical 
microarchitecture in patients with monoclonal gammopathy of undetermined significance. Blood, 123, 
647-649. 
 
7.Giles, SL, deSouza, NM, Collins, DJ, Morgan, VA, West, S, Davies, FE et al (2015) Assessing myeloma bone 
disease with whole-body diffusion-weighted imaging: comparison with x-ray skeletal survey by region and 
relationship with laboratory estimates of disease burden. Clinical Radiology, 70, 614-621. 
 
8.Giles, SL, Messiou, C, Collins, DJ, Morgan, VA, Simpkin, CJ, West, S et al (2014) Whole-Body Diffusion-
weighted MR Imaging for Assessment of Treatment Response in Myeloma. Radiology, 271, 785-794. 
 
9.Latifoltojar, A, Hall-Craggs, M, Rabin, N, Popat, R, Bainbridge, A, Dikaios, N et al (2017) Whole body 
magnetic resonance imaging in newly diagnosed multiple myeloma: early changes in lesional signal fat 
fraction predict disease response. Br J Haematol, 176, 222-233. 
 
10.Marti-Bonmati, L, Ramirez-Fuentes, C, Alberich-Bayarri, A, Ruiz-Llorca, C (2015) State-of-the-art of bone 
marrow imaging in multiple myeloma. Curr Opin Oncol, 27, 540-550. 
 
11.NICE 
(2016) 
Myeloma: 
diagnosis 
and 
management. 
NICE 
guideline 
[NG35]. 
https://http://www.nice.org.uk/guidance/ng35 Accessed February 2016 
 
12.Pawlyn, C, Fowkes, L, Otero, S, Jones, JR, Boyd, KD, Davies, FE et al (2016) Whole-body diffusion-
weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma? 
Leukemia, 30, 1446-1448. 

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13.Pianko, MJ, Terpos, E, Roodman, GD, Divgi, CR, Zweegman, S, Hillengass, J et al (2014) Whole-Body Low-
Dose Computed Tomography and Advanced Imaging Techniques for Multiple Myeloma Bone Disease. 
Clinical Cancer Research, 20, 5888-5897. 
 
14.Rafferty, J, Farr, L, James, T, Chase, D, Heinrich, J, Brady, M (2016) A new magnetic resonance-based 
technique for high-resolution quantification of amorphous and quasi-amorphous structures. Journal of The 
Royal Society Interface, 13, 
 
15.Rajkumar, SV, Dimopoulos, MA, Palumbo, A, Blade, J, Merlini, G, Mateos, MV et al (2014) International 
Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol, 15, e538-
548. 
 
16.Vasikaran, S, Cooper, C, Eastell, R, Griesmacher, A, Morris, HA, Trenti, T et al (2011) International 
Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine 
Position on bone marker standards in osteoporosis. Clin Chem Lab Med, 10.1515/cclm.2011.602 
 
 
 
 

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17. APPENDICES:  
17.1. 
 APPENDIX A: Schedule of assessments 
 
Type of Assessments 
Time of Assessments 
Baseline 
6 months (or clinical 
relapse/progression) 
Clinical history & Examination  
(Routine assessment) 
X 
X 
Bloods and urine biomarkers * 
X 
X 
Experimental MRI protocol 
X 
  X* 
DXA */** 
(Lumbar Spine and Hip Whole 
Body and VFA) 
X 
X 
Quality of Life Questionnaire (EQ-
5D) * 
X 
X 
DWMRI/DXA Patient Experience 
Questionnaire * 
X 
X 
 
*Not in healthy volunteers 
**If participants have already had a DXA scan at OUH NHS Foundation Trust within 2 months of the visit 
date then we will use that scan and not repeat the scan for that site. 
All procedures will happen during haematology clinic visit except DXA and MRI scan, which will be 
arranged for separate appointments. 
 
 
 
17.2. 
APPENDIX B: MRI SAFETY CHECKLIST 
See attached document <screening-form-volunteer-nov-2015.pdf> 
 

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