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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 to 99 years
• All sexes
• Healthy volunteers accepted
• Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

About this study

Official title: 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

Being tested

Diffusion Weighted Magnetic Resonance Imaging (DWMRI), DXA scan, Bloods and urine

Medical subject headings

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• 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.

• DXA scanOther

  Used to assess bone density

• Bloods and urineOther

  Samples will be taken to assess bone biomarkers

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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.

   Measured: At baseline

2. 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.

   Measured: At baseline

3. 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.

   Measured: At baseline

4. 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).

   Measured: At baseline

5. 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).

   Measured: At baseline

6. 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).

   Measured: At baseline

7. 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).

   Measured: At baseline

8. 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).

   Measured: At baseline

9. 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).

   Measured: At baseline

10. 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).

    Measured: At baseline

11. 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);
    3. Baseline DXA (Dual-energy X-ray Absorptiometry) BMD (Bone Mineral Density) at femoral neck.

    Measured: At baseline

12. 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.

    Measured: At baseline

13. 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.

    Measured: At baseline

14. 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.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted15 May 2019
2. Study start29 Mar 2018
3. Primary completion30 Dec 2020
4. Study completion30 Dec 2020

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for MyelomaStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.