Functional Imaging in Multiple Myeloma -PET/CT and Diffusion Weighted Imaging in Multiple Myeloma (FULIMA)

FULIMA - A Prospective Study of Dual Time PET/CT and Diffusion Weighted MRI in Multiple Myeloma

The FULIMA study is a two-center study at Odense University Hospital and Vejle Hospital, Denmark. The primary objective is to identify the optimal imaging technique for studies in multiple myeloma with focus on PET/CT and MRI.

By combining early (1 hour) and late (3 hours) 18F-2-fluoro-2-deoxy-D- fluorodeoxyglucose(18F-FDG)-PET/CT scans the investigators expect to see increased uptake of radioactive tracer and thus an improved ability to identify malignant tissue. A second tracer 18F-natrium-fluoride is used to explore early signs of bone remodeling. By using new software (ROVER) for interpreting PET data the investigators expect to obtain a quantitative measurement of total disease burden with less risk of misinterpretation of data.

Diffusion weighted MRI (DWI) is a new MRI technique which, like PET/CT, makes it possible quantitatively to calculate the overall disease activity and to give an early evaluation of response to chemotherapy. The study examines DWI for development and standardization.

To validate imaging findings and to explore the pathogenetic heterogeneity of multiple myeloma, the investigators perform CT guided biopsies from PET/ DWI positive sites. Pathoanatomical and immunohistochemical findings and gene expression data from positive sites are compared to random bone marrow. The question is whether disease heterogeneity may explain the lack of FDG uptake in bone marrow in some patients? To the extent that the FULIMA study produces useful data, the defined and standardized imaging techniques will form the basis of a larger prospective study at national level in Denmark.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Denmark
  • Odense C, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Prospective study with 60 patients referred to Haematological Department under the suspicion of having treatment demanding multiple myeloma. Patients will be included from two centres of Haematology.

Description

Inclusion Criteria:

1. Male or female subjects > 50 years at time of signing informed consent.
2. Subject under suspicion of having treatment demanding multiple myeloma in concordance with Danish cancer package criteria
3. Signed informed consent before performance of any study related procedures.
4. Subject is willing and able to comply with the protocol as judged by the investigator.

Exclusion Criteria:

1. Formerly treated multiple myeloma.
2. Known inflammatory disease, recent biological therapies or chemotherapy for non-malignant disease (less than 3 months prior to screening), clinically relevant active infection.
3. Concurrent or recent radiotherapy or surgery less than two weeks prior to screening
4. Glucocorticoid treatment exceeding 10 mg Prednisolone daily, less than two weeks prior to screening.
5. Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at an unacceptable risk if s/he were to participate in the study, e.g. high levels of liver-enzymes and creatinine.
6. Female subject is pregnant or breast feeding.
7. Serious co-morbidity, and other medical or psychiatric illness likely to interfere with participation in this clinical study.
8. Uncontrolled diabetes at the discretion of the investigator.
9. Known or prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer or in situ prostate cancer for which the subject has been disease free for at least three years.
10. POEMS syndrome (plasma cell dyscrasia with poly-neuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).
11. Exclusion according to MRI procedure (metal implants, claustrophobia, pace-maker).
12. Exclusion according to biopsy study (thrombocytes < 50x /L, activated partial thromboplastin time(APTT) > 40 sec, and international normalized ratio(INR) > 1.5)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple myeloma identified as bone disease, myeloma or plasmacytoma	A 1st complete set of imaging procedures is completed at time of diagnosis "baseline" (week 1-2) for all patients included in the study. The primary hypothesis that 3-hour FDG-PET / CT finds more malignant lesions than the current gold standard procedure, whole body x-ray(WBXR), together with CT and MRI. Concordance analysis will be done by summarizing comparisons of 3-hours FDG-PET/CT versus the remaining modalities. We measure a 95% Wilson-Score Confidence Interval (CI) to demonstrate that 3hours FDG-PET / CT find more malignant lesions than gold standard. This will be concluded at a significance level of 5% if the lower boundary of the 95% CI is larger than 30%.	"baseline"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease heterogeneity	CT guided or Ultra Sound guided biopsies from PET/ DWI positive sites. Pathoanatomical and immunohistochemical findings and gene expression data from positive sites are compared to random bone marrow.	Within 2 weeks after imaging procedures
Early signs of bone remodeling	18F-natrium-fluoride-PET/CT is performed at time of diagnosis (baseline) during week 1-2, after induction treatment and after end of treatment. We test if increased 18F-natrium-fluoride uptake is seen in bone sites where, according to CT and DWI, no abnormal bone remodeling is taking place and we observe the association between FDG-PET and fluoride-PET and markers of bone metabolism. We use descriptive statistics for number of bone sites with increased fluoride uptake, 95% Confidence interval	"baseline", after induction treatment and after end of treatment

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Brian Oestergaard, MD, Odense University Hospital

Publications and helpful links

General Publications

• Zadeh MZ, Seraj SM, Ostergaard B, Mimms S, Raynor WY, Aly M, Borja AJ, Arani LS, Gerke O, Werner TJ, Zhuang H, Revheim ME, Abildgaard N, Hoilund-Carlsen PF, Alavi A. Prognostic significance of 18F-sodium fluoride in newly diagnosed multiple myeloma patients. Am J Nucl Med Mol Imaging. 2020 Aug 25;10(4):151-160. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 23, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Myeloma; PET/CT; Functional Imaging; Diffusion Weighted MRI
• 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; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Body Weight
• Other Study ID Numbers: S-20120209; 13/24748 (Registry Identifier: Danish Dataprotection Agency)