The Development and Pilot Testing of a New MR Imaging Protocol to Quantify Myeloma Disease Burden and Bone Loss

NCT03951220 | Completed Results

• 1 other identifier: 12548
• Study Type: observational
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

In the proposed study, the investigators will aim to develop and pilot a Magnetic Resonance (MR) imaging protocol and assess its ability to achieve the following: quantification of tumour burden and bone loss, detecting longitudinal changes in tumour load with therapy and detecting longitudinal changes in microarchitecture with therapy. The investigators also aim to investigate whether bone loss is better, worse or the same with different imaging techniques. This will be investigated by correlating the DXA imaging data with Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) to see if it is possible to achieve quantifiable data of bone density.

Conditions

Myeloma; Monoclonal Gammopathy of Undetermined Significance (MGUS); Smouldering Myeloma

Outcome Measures

Primary Outcomes (14)

• Primary Outcome 1: Quantifying Tumour Burden [Correlations With Apparent Diffusion Coefficient (ADC) Measurements]

  Primary Objective 1: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This particular section analysed the correlation between the Apparent Diffusion Coefficient (ADC) measurements (from the Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) component of the sequences) of lytic bone lesions, with standard clinical correlates of tumour burden (serum paraprotein, and serum paraprotein-associated immunoglobulin level). The measurement of ADC from DW-MRI is further described by Messiou et. al. \[1\] \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.

  At baseline

• Primary Outcome 1: Quantifying Tumour Burden [Correlations With Myeloma Response Assessment and Diagnosis System (MY-RADS) Pattern of Disease]

  Primary Objective 1: To assess whether the novel MR protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. Participants' baseline novel MR scan was analysed by an expert radiologist, and pattern of disease was qualitatively classified using the MY-RADS (Myeloma Response Assessment and Diagnosis System) imaging recommendations, described in Figure 2 by Messiou et. al. \[1\]. This particular section analysed whether standard clinical correlate of tumour burden (serum paraprotein) differed by radiological pattern of disease (e.g., normal, focal, diffuse). \[1\] Messiou, Christina, et al. "Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS)." Radiology 291.1 (2019): 5-13.

  At baseline

• Primary Outcome 1: Quantifying Tumour Burden (Correlations With Bone Turnover Markers)

  Primary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve quantification of tumour burden in patients with new or relapsed myeloma at baseline assessment, compared to paraprotein levels alone. This section examined correlation between baseline bone biomarkers and baseline serum paraprotein in a pooled cohort of patients from Groups 1 and 2, using Spearman's Rank Correlation Coefficients.

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum P1NP (Procollagen Type 1 N-terminal Propeptide)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum P1NP (Procollagen Type 1 N-terminal Propeptide) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum CTX-1 (Collagen Cross-Linked C-Telopeptide Type I) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum ALP (Alkaline Phosphatase)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum ALP (Alkaline Phosphatase) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Sclerostin

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline serum sclerostin bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss - Inter-Group Differences in Baseline Serum Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. This particular section analysed the inter-group difference in baseline ratio between RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) and OPG (Osteoprotegerin) \[calculated as RANKL (pg/L) divided by OPG (pg/L)\] bone turnover marker levels, in patients from Groups 1a (new myeloma), 1b (relapsed myeloma), 1c (smouldering myeloma) and 2 (MGUS).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss (Inter-Biomarker Correlations)

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, Spearman's rank correlation coefficient was performed to assess correlations between all pairs of bone turnover markers, measured at baseline in a pooled cohort of participants from Groups 1 and 2: 1. P1NP (Procollagen Type 1 N-terminal Propeptide); 2. CTX-1 (Collagen Cross-Linked C-Telopeptide Type I); 3. ALP (Alkaline Phosphatase); 4. DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1); 5. Sclerostin; 6. Ratio of RANKL (Receptor Activator of Nuclear Factor Kappa-Β Ligand) to OPG (Osteoprotegerin).

  At baseline

• Primary Outcome 2: Quantifying Bone Loss [Correlations Between Bone Turnover Markers, DXA (Dual-energy X-ray Absorptiometry) and ADC (Apparent Diffusion Coefficient)]

  Primary Outcome 2: To assess whether the novel magnetic resonance (MR) protocol and exploratory bone turnover markers can improve quantification of bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy Of Uncertain Significance (MGUS) at baseline assessment, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone turnover markers alone. In this particular section, in a pooled cohort of participants from Groups 1 and 2, Spearman's rank correlation coefficients were calculated between all baseline bone turnover biomarkers and: 1. Baseline novel MR Apparent Diffusion Coefficient (ADC) measurements; 2. Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at lumbar spine (L1-4); 2\) Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at femoral neck.

  At baseline

• Primary Outcome 1+2: Quantifying Tumour Burden (Total Spinal 'Hole' Volume)

  * This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for lytic lesions (holes). * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel MR scan, due to technical challenges.

  At baseline

• Primary Outcome 1+2: Quantifying Tumour Burden (Total Spinal 'Collapse' Volume)

  * This was intended as a novel end-point produced by OCMR scientists, in which high-resolution 3D imaging of the spine and pelvis are analysed for the extent of vertebral collapse. * Unfortunately, we were unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel magnetic resonance (MR) scan, due to technical challenges.

  At baseline

• Primary Outcome 1+2: Quantifying Tumour Burden [Osteotronix Fine Structural Analysis (FSA), Trabecular Wall Thickness]

  * Osteotronix' fineSA® (Fine Structural Analysis, FSA) technology extracts microstructural information from Magnetic Resonance Imaging (MRI) data sets, 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 \[Rafferty et al, 2016\]. * In this study, we had collected data during the novel MR protocol at both baseline and follow-up time points. However, we were unable to complete analysis of the FSA metrics, because of disruptions due to COVID-19, therefore the results have not been possible to report.

  At baseline

Secondary Outcomes (8)

• Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) vs IMWG (International Myeloma Working Group) Response Group Classification]

  Comparison between baseline and follow-up at 6 months.

• Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [MY-RADS RAC (Myeloma Response Assessment and Diagnosis System Response Assessment Classification) vs % Change in ADC (Apparent Diffusion Coefficient)]

  Comparison between baseline and follow-up at 6 month

• Secondary Outcome 1: Detect Longitudinal Changes in Tumour Load With Therapy [% Change in ADC (Apparent Diffusion Coefficient) vs IMWG (International Myeloma Working Group) Response Group Classification]

  Comparison between baseline and follow-up at 6month

• Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (% Change in Bone Turnover Markers)

  Comparison between baseline and follow-up at 6month

• Secondary Outcome 2: Detect Longitudinal Changes in Bone Microarchitecture With Therapy (Correlations Between % Change in Bone Turnover Markers)

  Comparison between baseline and follow-up at 6month

Study Arms (3)

Group 1- Myeloma

Participants will be recruited at the point of either diagnosis or relapse. Any standard investigations that the clinician deems necessary will be carried out. Following recruitment, participants will undergo the first study appointment, the experimental combined MR imaging protocol, the DXA imaging scan and the bone biomarker blood and urine tests. This will be repeated at 6 months.

Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI); Other: DXA scan; Other: Bloods and urine

Group 2- MGUS

Participants will be recruited at the point of either diagnosis or relapse. Any standard investigations that the clinician deems necessary will be carried out. Following recruitment, participants will undergo the first study appointment, the experimental combined MR imaging protocol, the DXA imaging scan and the bone biomarker blood and urine tests. This will be repeated at 6 months.

Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI); Other: DXA scan; Other: Bloods and urine

Group 3- Healthy Volunteers

Participants will have the experimental combined MR imaging.

Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI)

Interventions

Diffusion Weighted Magnetic Resonance Imaging (DWMRI) OTHER

Using the expertise of the Oxford Centre For Clinical Magnetic Resonance Research (OCMR) for imaging protocol development, and the new Fine Structural Analysis (FSA, Osteotronix Ltd, formerly Acuitas Medical) bone density quantification MRI method (Rafferty et al 2016), we will test a single protocol which combines three emerging experimental imaging sequences into a simple, non-invasive whole body imaging protocol to quantify disease burden and bone disease. 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.

Group 1- Myeloma; Group 2- MGUS; Group 3- Healthy Volunteers

DXA scan OTHER

Used to assess bone density

Group 1- Myeloma; Group 2- MGUS

Bloods and urine OTHER

Samples will be taken to assess bone biomarkers

Group 1- Myeloma; Group 2- MGUS

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants in Groups 1 \& 2 will be recruited via the Haematology Outpatients clinic in Churchill Hospital. Group 3 participants will be recruited from the community

You may qualify if:

• Participant is able to and willing to give informed consent for participation in the study.
• Male or Female, aged 18 years or above.
• 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).

You may not qualify if:

• Those who are unable or unwilling to give informed consent.
• 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.
• Signs of Spinal Cord Compression.
• Patients with documented metastatic lesions from another type of malignancy.
• Known contraindication for a MRI scan, including unacceptable pain on lying flat for 1 hour.

Sponsors & Collaborators

• Oxford University Hospitals NHS Trust: lead
• Amgen: collaborator

Study Sites (1)

Churchill Hospital

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bloods and urine

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma

Interventions

Absorptiometry, Photon; Urination

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Limitations and Caveats

* Unable to collect data for the total spinal hole volume and total spine collapse volume at the point of novel MR scan, due to technical challenges. * Whilst data collection is complete, there were delays in completing the analysis for Osteotronix FSA data due to disruptions with COVID-19, therefore the results have not been reported in this Study Report at time of submission. However, there is ongoing engagement with Osteotronix to complete this analysis.

Results Point of Contact

• Title: Gaurav Agarwal
• Organization: University of Oxford

gaurav.agarwal@medsci.ox.ac.uk

07826636655

Study Officials

• Karthik Ramasamy

  University of Oxford Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 15, 2019
• Study Start: March 29, 2018
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: August 19, 2025
• Results First Posted: August 19, 2025

Record last verified: 2025-07

Locations

GB (1)