Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01171430 |
| Other study ID # |
P081236 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2010 |
| Est. completion date |
February 2019 |
Study information
| Verified date |
November 2020 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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, i.e. 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 n°5)or younger, high-dose therapy (HDT) followed by
treatment (amendment n°3) 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 mg/m2 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 CR/VGPR, 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.
