Churchill Hospital
Oxford, Oxfordshire, OX3 7LE, United Kingdom
NCT Number: NCT03951220
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.
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Notify Me18 year–99 year
All sexes
Observational
Oxford, Oxfordshire, OX3 7LE, United Kingdom
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.
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), the investigators 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. 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.
The investigators 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.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
(All Groups):
Inclusion criteria
(Groups 1 and 2):
Exclusion criteria
(All Groups):
Exclusion criteria
(Groups 1 and 2):
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.
Used to assess bone density
Samples will be taken to assess bone biomarkers
Time frame: At baseline
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.
Time frame: At baseline
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.
Time frame: At baseline
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.
Time frame: At baseline
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).
Time frame: At baseline
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).
Time frame: At baseline
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).
Time frame: At baseline
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).
Time frame: At baseline
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).
Time frame: At baseline
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).
Time frame: At baseline
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:
Time frame: At baseline
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:
Time frame: At baseline
Time frame: At baseline
Time frame: At baseline
Time frame: Comparison between baseline and follow-up at 6 months.
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone.
This section compared two indicators of therapy response:
Ref:
Time frame: Comparison between baseline and follow-up at 6 month
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone.
This section compared two indicators of therapy response:
Ref:
[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
Time frame: Comparison between baseline and follow-up at 6month
Secondary Objective 1: To assess whether the novel Magnetic Resonance (MR) protocol can improve detection of longitudinal changes in tumour burden in patients with new or relapsed myeloma during therapy, compared to the International Myeloma Working Group (IMWG) Response Group classification alone.
This section compared two indicators of therapy response:
Ref:
Time frame: Comparison between baseline and follow-up at 6month
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone.
This section examined whether longitudinal change in bone turnover markers differed by chemotherapy responders vs non-responders.
Time frame: Comparison between baseline and follow-up at 6month
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone.
This particular section examined the correlation between longitudinal changes in bone turnover markers between one another (calculated as a ratio of follow-up measurement divided by baseline measurement). Spearman's rank correlation was performed for the longitudinal % change between different biomarkers, to assess the relationship between longitudinal changes in these measures.
Time frame: Comparison between baseline and follow-up at 6month
Secondary Objective 2: To assess whether the novel Magnetic Resonance (MR) protocol and exploratory bone biomarkers can improve detection of longitudinal changes in bone loss in patients with myeloma (new, relapsed, smouldering) and Monoclonal Gammopathy of Undetermined Significance (MGUS) during therapy, compared to Dual-energy X-ray Absorptiometry (DXA) and established bone biomarkers alone.
This section examined the correlation (using Spearman's Rank Correlation Coefficient) between longitudinal changes (expressed as a ratio of follow-up / baseline of paired measurements) in bone turnover markers and:
Time frame: At baseline and six months
Secondary Objective 3: To assess how quality of life compares between groups and longitudinally in patients with myeloma, Monoclonal Gammopathy of Undetermined Significance (MGUS), and healthy volunteers.
The EuroQol 5-Dimension (EQ-5D) assess the mobility, self-care, usual activities, pain/discomfort, anxiety and depression on a 5-point scale, in which a lower score represents better quality of life (1 = 'no problems', 5 = maximum problems, for each domain). The second part of the EQ-5D assess health on a scale where 100 is the best health and 0 is the worst health.
Time frame: At baseline and six months
This questionnaire assesses the experience of the Novel Magnetic Resonance (MR) and Dual-energy X-ray Absorptiometry (DXA) scans. Answers were recorded on a 5 point Likert scale where the lower number represents a better outcome.
Scale descriptors:
Q1 (Overall Experience): 1 (Very comfortable)/ 2 (Comfortable)/ 3 (Neither comfortable or uncomfortable)/ 4 (Uncomfortable)/ 5 (Very uncomfortable) Q2 (Adverse Effects): 1 (YES) / 0 (NO) Q3 (Length of Time): 0 (Too short) / 1 (Just right) / 2 (Too long) Q4 (Pain/Discomfort): 1 (No Increase)/ 2 (Mild Increase)/ 3 (Moderate Increase)/ 4 (High Increase)/ 5 (Severe Increase) Q5 (Likely to Reparticipate): 0 (Extremely Unlikely) / 1 (Unlikely) / 2 (Neither Likely or Unlikely) / 3 (Likely) / 4 (Extremely Likely) Q6 (How similar to expectations): 1 (YES) / 0 (NO) Q7 (Comfort with Staff): 1 (YES) / 0 (NO)
Oxford University Hospitals NHS Trust
Other
The Development and Pilot Testing of a New Magnetic Resonance (MR) Imaging Protocol to Quantify Both Myeloma Disease Burden and Associated Bone Loss
Acronym: LOOMIS
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