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

The Development and Pilot Testing of a New Magnetic Resonance (MR) Imaging Protocol to Quantify Both Myeloma Disease Burden and Associated Bone Loss

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.

Study Overview

• Status: Completed
• Conditions: Myeloma; Smouldering Myeloma; Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Intervention / Treatment: Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI); Other: DXA scan; Other: Bloods and urine

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Churchill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

Inclusion Criteria (All Groups):

• Participant is able to and willing to 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).

Exclusion Criteria (All Groups):

• 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.

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, including unacceptable pain on lying flat for 1 hour.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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); 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.; Other: DXA scan; Used to assess bone density; Other: Bloods and urine; Samples will be taken to assess bone biomarkers
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); 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.; Other: DXA scan; Used to assess bone density; Other: Bloods and urine; Samples will be taken to assess bone biomarkers
Group 3- Healthy Volunteers; Participants will have the experimental combined MR imaging.	Other: Diffusion Weighted Magnetic Resonance Imaging (DWMRI); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. DW-MRI: ADC change	This will be calculated using the DW-MRI scans at both baseline and follow up	At baseline and six months
2. Total spinal 'hole' volume	This will be calculated using the DW-MRI scans at both baseline and follow up 3. Total spine 'collapse' volume 4. FSA: trabecular wall thickness (Rafferty et al, 2016)	At baseline and six months
3. Total spine 'collapse' volume	This will be calculated using the DW-MRI scans at both baseline and follow up	At baseline and six months
4. FSA: trabecular wall thickness	This will be calculated using the DW-MRI scans at both baseline and follow up	At baseline and six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detect longitudinal changes in tumour load with therapy	All imaging will be repeated at 6 months. The scans will be analysed to see the difference in number of tumour sites before and after therapy (at baseline and at six months). Scans at both time points will be compared to see the difference in ADC, total spinal 'hole' volume, total spine 'collapse' volume and the trabecular wall thickness.	At 6 months
Assess participants Quality of Life (EQ-5D) throughout the study	Assess participants Quality of Life (EQ-5D) throughout the study life using data from the EQ-5D-5L questionnaire. The EQ-5D assess the mobility, self-care, usual activities, pain/discomfort, anxiety and depression via 3 options ranging from 'no problems' to 'unable to do/extreme pain/anxious'. The second part of the EQ-5D assess health on a scale where 100 is the best and 0 is the worst.	At baseline and six months
Assess participants experience of the novel MR imaging scan	Analyse participants experience of the novel MR imaging using data from MRI/DXA scanning questionnaire. This questionnaire assesses the experience of the novel imaging scan, whether any pain/discomfort was experienced. These answers are recorded on a 5 point likert scale where the lower number represents a better outcome.	At baseline and six months

Collaborators and Investigators

• Sponsor: Oxford University Hospitals NHS Trust
• Collaborators: Amgen
• Investigators: Principal Investigator: Karthik Ramasamy, University of Oxford Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): December 30, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: 12548

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No