Whole Body Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) in Multiple Myeloma (MMY-MRI-08)

Comparison of Whole Body Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) With Skeletal X-Ray and MRI of the Spine for the Assessment of Bone Disease in Multiple Myeloma

Bone disease in multiple myeloma (MM) is routinely assessed by skeletal X-ray (XR) and magnetic resonance of the spine (S-MRI). Diffusion-weighted MRI (DW-MRI) is a functional MRI that detects water diffusion through cells. This prospective phase II study compared whole-body DW-MRI with XR and S-MRI for the assessment of MM bone lesions.

METHODS. Thirty-six consecutive symptomatic patients at diagnosis or at relapse performed XR, S-MRI, whole-body MRI, and whole-body DW-MRI before treatment, after treatment, and 6 months after treatment. A substudy evaluated 12 asymptomatic patients at diagnosis, after 6 and 12 months. Radiology exams were independently read by 3 experienced radiologists, and the techniques were compared by the count of segments with focal lesions (FL) (>=5mm).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Other: DW-MRI

Detailed Description

PROTOCOL SYNOPSIS -

Study Type Monocentric prospective clinical trial Study Object Comparison of Whole Body Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) with skeletal X-Ray and MRI of the spine for the assessment of bone disease in Multiple Myeloma (MM) Objectives

Primary objective 1) To assess whether DW-MRI can detect a higher number of bone lesions than standard X-Ray and MRI of the spine in Stage I-III symptomatic MM patients Secondary objectives

1. To assess whether the change in the number of lesions detected with DW-MRI at follow up correlate with disease response to therapy
2. To assess whether the change in the number of lesions detected with DW-MRI at follow up correlate with time to re-treatment (TTR)
3. To assess whether DW-MRI detects a higher number of bone lesions than Whole Body Magnetic Resonance Imaging (WB-MRI) Exploratory objective

1) To assess whether DW-MRI detects more bone lesions than standard X-Ray and MRI of the spine in Stage I asymptomatic MM patients at diagnosis not requiring treatment Study population and design The study population consists consecutive Stage I-III (Durie and Salmon) symptomatic Multiple Myeloma at the start of the first-line treatment or at relapse after disease response (CR or PR) lasting at least 6 months.

Study procedures

The patients will perform a DW-MRI, a whole body MRI (WB-MRI), a MRI of the spine and a plain skeletal X-Ray with clinical and laboratory evaluations with the following timing:

1. Patients at first-line treatment for MM:

   1. Within 15 days before the start of the treatment
   2. Within one month after the end of the first-line treatment
   3. 6 months after the end of the first-line treatment

2. Patients at relapse after disease response (CR or PR) lasting at least 6 months

   1. At relapse
   2. Within 15 days after the end of the treatment of relapse
   3. 6 months after the end of the treatment of relapse The DW-MRI, WB-MRI and MRI of the spine will be performed in the same session. Each DW-MRI, WB-MRI, MRI of the spine and skeletal X-Ray will be independently read and interpreted by two radiologists with proven experience in MM. Each radiologist will read and interpret the exams performed; the lecture of each exam will be blinded; the identity of the patient and the result of the lecture by the other radiologist will be blinded. In case the number of lesions detected by the radiologists would not match, the number of lesions will be determined by consensus between the radiologists.

In case of more bone lesions detected by DW-MRI compared to MRI and skeletal X-Ray, a PET scan will be performed.

Sample size The trial is designed to demonstrate a 30% increase in the number of bone lesions detected by DW MRI (experimental method) as compared to standard X-Ray and MRI of the spine (standard method). To detect such an effect size with a one sided Student t test at the 5% significance and 90% power, 27 patients need to be investigated, that we round to 30 to account for a 10% patient drop out. A midcourse sample size reassessment according to the approach proposed by Proschan, Liu & Hunsberger (2003) will use interim data from the first 20 patients to decide to either maintain or increase the original sample size in a range between 30 and 60 patients, depending on whether the estimated effect size is aligned or not with the anticipated value.

Substudy The substudy for the assessment of the exploratory objective will enroll 10 consecutive Stage I (Durie and Salmon) asymptomatic MM patients at diagnosis not requiring treatment. The patients will perform the radiological and laboratory evaluations at diagnosis and at 6 and 12 months after diagnosis.

Study duration The estimated duration of enrolment ranges between 15 and 30 months. The follow up duration is 6 months. The estimated total duration of the study is 3 years. A midcourse assessment of interim data is planned at the end of the first phase of enrolment (20 patients) to determine the sample size of the second phase.

Selection criteria Inclusion criteria

• Age ≥18 years
• Stage I-III (Durie-Salmon) symptomatic MM at the start of first-line treatment or at relapse after disease response (CR or PR) lasting at least 6 months
• Stage I (Durie-Salmon) asymptomatic MM at diagnosis not requiring treatment (substudy for assessment of exploratory objectives)
• Written informed consent Exclusion criteria
• Pregnancy or lactation
• Active secondary malignancy
• Type I hypersensitivity or anaphylactic reactions to Gadolinum contrast agent
• Mental disorders including claustrophobia (ICD 10, F40.2)
• Electronically, magnetically and mechanically activated implants
• Ferromagnetic or electrically operated active devices like automatic cardioverter defibrillators
• Cardiac pacemakers
• Metallic splinters in the eye
• Ferromagnetic haemostatic clips in the central nervous system (CNS) or in the body
• Cochlear implants or stapedial implants
• Insulin pumps and nerve stimulators
• Prosthetic hearth valves Study Procedures at baseline • Medical history and physical examination
• Cell blood count and differential
• Clinical laboratory evaluations: Na+, K+, Ca2+, BUN, creatinine, LDH, PCRq, uric acid, AST, ALT, GGT, ALP, bilirubin (total and direct/indirect), albumin, protein electrophoresis, IgA, IgG, IgM, serum immunofixation, serum free light chains, 24h proteinuria, 24h Bence-Jones proteinuria, urine immunofixation, beta2microglobulin; HIV-Ab, HBsAg, HCV-Ab; pregnancy test for females of childbearing potential
• ECG
• DW-MRI (whole body Diffusion Weighted Magnetic Resonance Imaging)
• WB-MRI (Whole Body Magnetic Resonance Imaging)
• Skeletal survey including skull, cervical, thoracic and lumbar spine, pelvis, right and left humerus and femur, sternum and bilateral ribs
• MRI of the spine
• Bone marrow biopsy and bone marrow aspirate for morphology, FISH analysis for del(13), t(4:14), t(11:14), t(14:16), del(17), and flow cytometric immunophenotyping of CD138+, CD19+, CD28+ and CD117+.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:•

.Age ≥18 years , < 80 years

• Stage I-III (Durie-Salmon) symptomatic MM at the start of first-line treatment or at relapse after disease response (CR or PR) lasting at least 6 months
• Stage I (Durie-Salmon) asymptomatic MM at diagnosis not requiring treatment (substudy for assessment of exploratory objectives)
• Written informed consent

Exclusion Criteria:

• Pregnancy or lactation
• Active secondary malignancy
• Type I hypersensitivity or anaphylactic reactions to Gadolinum contrast agent
• Mental disorders including claustrophobia (ICD 10, F40.2)
• Electronically, magnetically and mechanically activated implants
• Ferromagnetic or electrically operated active devices like automatic cardioverter defibrillators
• Cardiac pacemakers
• Metallic splinters in the eye
• Ferromagnetic haemostatic clips in the central nervous system (CNS) or in the body
• Cochlear implants or stapedial implants
• Insulin pumps and nerve stimulators
• Prosthetic hearth valves

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: DW- MRI; The patients will perform the DW-MRI, WB-MRI and MRI of the spine in the same session with the following timing: Patients at first-line treatment for MM:Within 15 days before the start of the treatmentWithin one month after the end of the first-line treatmentSix (6) months after the end of the first-line treatment; Patients at relapse after disease response (CR or PR) lasting at least 6 monthsAt relapseWithin 15 days after the end of the treatment of relapseSix (6) months after the end of the treatment of relapse Each DW-MRI, WB-MRI, MRI of the spine and skeletal X-Ray will be independently read and interpreted by two radiologists with proven experience in MM. .

Other: DW-MRI; MRI imaging with diffusion weighted sequences of the whole body; Other Names: Whole Body Diffusion Weighted Magnetic Resonance Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1) To assess whether DW-MRI can detect a higher number of bone lesions than standard X-Ray and MRI of the spine	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
1) To assess whether the change in the number of lesions detected with DW-MRI at follow up correlate with disease response to therapy	12 months
2) To assess whether the change in the number of lesions detected with DW-MRI at follow up correlate with time to re-treatment (TTR)	12 months
3) To assess whether DW-MRI detects a higher number of bone lesions than Whole Body Magnetic Resonance Imaging (WB-MRI)	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) To assess whether DW-MRI detects more bone lesions than standard staging procedures in Stage I asymptomatic MM patients at diagnosis not requiring treatment	Exploratory objective	12 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Paolo Corradini, Professor, Fondazione IRCCS Istituto Nazionale dei Tumori , Via Venezian, 1- 20133 Milano, Italy

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: April 9, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (ESTIMATE): April 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 11, 2013
• Last Update Submitted That Met QC Criteria: April 9, 2013
• Last Verified: April 1, 2013

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; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: MMY-MRI-08