Ignite Creation Date:
2024-05-05 @ 10:44 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01171430
Status:
COMPLETED
Last Update Posted:
2020-11-20
First Post:
2010-06-23
Brief Title:
WB-DCE-MRI in Multiple Myeloma as an Independent Prognostic Factor for Disease-free Survival
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Assessment of Dynamic Contrast Enhanced Whole Body MRI DCE-WB-MRI as Independent Prognostic Factor for Disease-free Survival in Multiple Myeloma After Intensification Therapy and Autologous Stem Cell Transplantation Suppressed by Amendment n3
Status:
COMPLETED
Status Verified Date:
2020-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EVALICEMM
Brief Summary:
The main objective of this study is to examine if absence of a satisfactory response on DCE-WB-MRI see MR criteria of responders section after completion of HDT followed by autologous stem-cell transplantation ASCT is an independent prognostic factor for EFS in patients with MM compared with established ones including beta2-microglobulin and cytogenetic abnormalities Secondary objectives are to examine if the microcirculation parameters obtained from baseline DCE-WB-MRI have prognostic significance and to examine if early DCE-WB-MRI performed after the induction HDT and before ASCT might also provide independent prognostic information for patient outcome which might help in patient stratification and be integrated into the response criteria in the future
Detailed Description:
Introduction Bone marrow angiogenesis is increased in multiple myeloma MM and is an important prognostic factor for survival Newly diagnosed MM patients have higher microvessel density MVD than controls on bone marrow biopsies In addition patients with higher MVD receiving conventional chemotherapy or high-dose therapy with autologous stem cell transplantation have shorter median overall survival than those with lower MVD by using the median MVD as the cutoff In a study with 81 patients with MM treated with thalidomide with or without dexamethasone MVD decreased significantly in responders while no significant change in MVD was seen in those failing to respond to thalidomide
Microcirculation variables derived from dynamic contrast-enhanced magnetic resonance DCE-MR imaging ie maximum enhancement and the exchange rate constant correlate well with the histologic infiltration grade MVD and serum markers of disease activity Recently the maximal amplitude of lumbar bone marrow enhancement on DCE-MR examination has been identified as a prognostic variable for event-free survival EFS in progressive MM These parameters may serve as non-invasive surrogate biomarkers for determining prognosis and for assessing treatment response in myeloma patients However these studies used techniques which were limited to a maximal 400-mm field of view whereas myeloma can involve the bone marrow focally diffusely throughout the body or even outside the marrow space With the advancement of MR technologies unenhanced whole-body MR imaging has proven more reliable than radiological skeletal survey and whole-body multidetector computed tomography in patients with MM
Recently whole-body single-phase contrast-enhanced sequence was applied in combination with unenhanced sequences for the detection of myeloma lesions However single-phase post-contrast MR examinations do not provide detailed enhancement curves and this limitation possibly hinders the assessment of disease activity On the other hand segmental dynamic MR examinations do not enable assessment of the dynamic enhancement of focal lesions in different bone marrow segments That was the reason which led us to develop a dynamic contrast-enhanced whole-body magnetic resonance imaging DCE-WB-MRI protocol which was never explored in MM
The treatment of patients with MM was largely palliative until with the advent of high-dose melphalan high rates of complete response CR could be obtained For previously untreated patients aged 70 years amendment n5or younger high-dose therapy HDT followed by treatment amendment n3 with growth-factor-mobilized peripheral-blood stem cells PBSCs have been demonstrated superior to conventional chemotherapy with not only higher CR rates but also significantly extending EFS and overall survival Recently the International Myeloma Working Group proposed new uniform response criteria to facilitate precise comparisons between new evolving treatment strategies As a functional imaging providing parameters related to angiogenesis and disease activity in MM DCE-WB-MRI might provide additional information on prognostically important microcirculation variables on a whole-body scale It might also prove helpful in assessing treatment response and further treatment strategy decision for patients with oligo- or nonsecretory disease
Study Description
Treatment regimen the HDT followed by ASCT with PBSCs will be given The ASCT will be conditioned by high-dose melphalan HDMel 200 mgm2 with or without bortezomib following the actual guidelines
Response assessment clinical response will be assessed on the same day of each post-treatment MR examination and recorded according to the uniform response criteria After completion of HDT followed by ASCT patients will be followed every 4 months for the first two years and every 6 months thereafter for a total of at least 5 years An event is defined as disease progression relapse from clinical CRVGPR or death from any cause
DCE-WB-MRI schedule three MR examinations will be performed the first at diagnosis and before initiation of chemotherapy the second after induction chemotherapy and before ASCT and the third exam three months after ASCT The results of each DCE-WB-MRI will not influence further treatment strategy
MR Criteria of Responders
A satisfactory response on DCE-WB-MRI is defined by the presence of a maximal percentage of bone marrow enhancement below 100 All focal lesions if present must not present an early enhancement but a progressive delayed type maximal enhancement
Microcirculation variables derived from dynamic contrast-enhanced magnetic resonance DCE-MR imaging ie maximum enhancement and the exchange rate constant correlate well with the histologic infiltration grade MVD and serum markers of disease activity Recently the maximal amplitude of lumbar bone marrow enhancement on DCE-MR examination has been identified as a prognostic variable for event-free survival EFS in progressive MM These parameters may serve as non-invasive surrogate biomarkers for determining prognosis and for assessing treatment response in myeloma patients However these studies used techniques which were limited to a maximal 400-mm field of view whereas myeloma can involve the bone marrow focally diffusely throughout the body or even outside the marrow space With the advancement of MR technologies unenhanced whole-body MR imaging has proven more reliable than radiological skeletal survey and whole-body multidetector computed tomography in patients with MM
Recently whole-body single-phase contrast-enhanced sequence was applied in combination with unenhanced sequences for the detection of myeloma lesions However single-phase post-contrast MR examinations do not provide detailed enhancement curves and this limitation possibly hinders the assessment of disease activity On the other hand segmental dynamic MR examinations do not enable assessment of the dynamic enhancement of focal lesions in different bone marrow segments That was the reason which led us to develop a dynamic contrast-enhanced whole-body magnetic resonance imaging DCE-WB-MRI protocol which was never explored in MM
The treatment of patients with MM was largely palliative until with the advent of high-dose melphalan high rates of complete response CR could be obtained For previously untreated patients aged 70 years amendment n5or younger high-dose therapy HDT followed by treatment amendment n3 with growth-factor-mobilized peripheral-blood stem cells PBSCs have been demonstrated superior to conventional chemotherapy with not only higher CR rates but also significantly extending EFS and overall survival Recently the International Myeloma Working Group proposed new uniform response criteria to facilitate precise comparisons between new evolving treatment strategies As a functional imaging providing parameters related to angiogenesis and disease activity in MM DCE-WB-MRI might provide additional information on prognostically important microcirculation variables on a whole-body scale It might also prove helpful in assessing treatment response and further treatment strategy decision for patients with oligo- or nonsecretory disease
Study Description
Treatment regimen the HDT followed by ASCT with PBSCs will be given The ASCT will be conditioned by high-dose melphalan HDMel 200 mgm2 with or without bortezomib following the actual guidelines
Response assessment clinical response will be assessed on the same day of each post-treatment MR examination and recorded according to the uniform response criteria After completion of HDT followed by ASCT patients will be followed every 4 months for the first two years and every 6 months thereafter for a total of at least 5 years An event is defined as disease progression relapse from clinical CRVGPR or death from any cause
DCE-WB-MRI schedule three MR examinations will be performed the first at diagnosis and before initiation of chemotherapy the second after induction chemotherapy and before ASCT and the third exam three months after ASCT The results of each DCE-WB-MRI will not influence further treatment strategy
MR Criteria of Responders
A satisfactory response on DCE-WB-MRI is defined by the presence of a maximal percentage of bone marrow enhancement below 100 All focal lesions if present must not present an early enhancement but a progressive delayed type maximal enhancement
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None