The aim of this project is to validate 3 novel biomarkers (FDG PET/CT, WES and NGF). The utilization goal is to implement these biomarkers afterwards in clinical practice to rationalize treatment strategies. The primary objective is to validate the…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is to evaluate the prognostic value of
FDG-PET combined with NGF in patients achieving VGPR or better after induction
chemotherapy and ASCT and before lenalidomide maintenance therapy. We
hypothesize that only patients who have no evidence of disease on both NGF and
FDG-PET have a durable response with a 2y PFS of 90% compared to 50% in pts who
have evidence of disease on at least one modality. PFS is defined as the time
from achieving >= VGPR and confirmation of absence of MRD (landmark) to first
documentation of objective progressive disease or death due to any cause,
whichever occurs first. The <10-5 MRD level is used to define BM-NGF
MRD-negativity. A Deauville score=3 threshold will be used to define FDG-PET
MRD-negativity, but alternatives will also be evaluated (other DS, more
quantitative measures like SUV)
Secondary outcome
The secondary endpoint is to implement WES and Radiomics at baseline to improve
risk-stratification.
Background summary
Multiple myeloma (MM) is defined by a malignant proliferation of plasma cells
in the bone marrow (BM). It is the second most common hematological malignancy
after lymphomas and accounts for 1% of all cancers. According to data from the
Belgian Cancer Registry, each day two patients receive a diagnosis of MM in
Belgium.
Currently, newly diagnosed MM (NDMM) patients who are fit for intensive
treatment can obtain durable clinical responses, including complete responses
(CR). Nevertheless, there is still a population of high-risk NDMM patients that
fail to achieve durable responses. The prognosis of these patients,
representing 20% of the patients, is particularly grim, with a median overall
survival (OS) of only 2 years compared to 7-10 years for the overall
transplant-eligible group. Upfront identification of this high-risk population
is critically important, because these patients may benefit from more
intensified treatment approaches or from treatment with novel agents.
Combination of these techniques, FDG-PET/CT, CXCR4-PET/CT, NGF and WES, could
help identify these high-risk vs low-risk patients and could help in defining
patient specific treatment strategies
Study objective
The aim of this project is to validate 3 novel biomarkers (FDG PET/CT, WES and
NGF). The utilization goal is to implement these biomarkers afterwards in
clinical practice to rationalize treatment strategies.
The primary objective is to validate the use of FDG-PET/CT imaging combined
with BM-NGF to refine the definition of MRD after ASCT; if validated, this new
biomarker combination could be used for a more risk-adapted approach after ASCT
to determine which pts might benefit most from lenalidomide maintenance and to
shorten the duration of maintenance in pts with persistence of MRD-negativity.
As secondary objective, we will explore the use of PET radiomics and WES prior
to the start of treatment to better discriminate between high-risk and
standard-risk pts, which is important to shift from the current *one-
size-fits-all* therapeutic approach to a more risk-adapted approach
Study design
Observational study - no intervention.
This study includes newly diagnosed multiple myeloma patients who will receive
standard of care. This standard of care includes induction chemotherapy
followed by autologous stem cell transplantation (ASCT) followed by
lenalidomide maintenance therapy. Prior to the start of treatment, all patients
will undergo a whole body FDG-PET/LDCT. An aliquot of the BM sample will be
used for WES. Patients who achieve at least a very good partial response
(VGPR) according to the IMWG response criteria, will start lenalidomide
maintenance therapy 3 months after ASCT. Prior to the start of maintenance, PET
imaging with FDG will be repeated when positive at baseline. MRD status will be
defined based on NGF (Euroflow protocol) on BM aspirate before and after 1 and
2 years of maintenance therapy. During maintenance therapy, patient will
undergo follow-up visits. These visits will depend on the center/treating
doctor, but should be recorded in the eCRF at least once every 3 months. These
visits will include a clinical examination, biochemical analysis, as well as
serum and urine electrophoresis. In the absence of toxicity, maintenance
treatment will be continued until biochemical or clinical progressive disease
according to IMWG criteria, irrespective of the PET or NGF results.
If a patient shows relapse (PD) during lenalidomide maintenance therapy, a bone
marrow examination will be performed and a bone marrow aspirate will be taken
for WES-analysis.
In addition, patients can also be included after ASCT, and prior to the start
of lenalidomide maintenance therapy. Remark: patients can only be included when
a baseline FDG PET scan is available showing FDG avid disease (= at least 1
focal lesion DS4). WES and NGF data at baseline can be performed by using
leftover bone marrow material (if leftover material is available). It is
expected that no baseline CXCR4-PET scan will be available for this subgroup of
patients.
Study burden and risks
As this is an observational study, no additional risks are associated with
participation.
Prinsstraat 13
Antwerpen 2000
NL
Prinsstraat 13
Antwerpen 2000
NL
Listed location countries
Age
Inclusion criteria
- Transplant eligible newly diagnosed multiple myeloma based on current IMWG
criteria and scheduled for induction therapy followed by autologous stam cell
transplantation.
- Baseline 18F-FDG PET/CT scan should be performed. Prior to start of
treatment, or within 7 days after the start. the scan should show FDG avid
disease.
- WHO performance status 0-2 (WHO >2 can be allowed if due to underlying
disease and after discussion with the physician)
- Age 18 years or older
- life expectancy > 12 months, based on clinical judgement.
- achieving at least VGPR after induction therapy and ASCT according to the
standard IMWG response criteria.
- received at least one (28-day) cycle of lenalidomide as maintenance therapy
after ASCT. No new therapy can be given until clinical relapse.
Exclusion criteria
- any physical or physiological condition that may affect adherence to the
study protocol (severe claustrophobia, inability to lie still for 30 minutes)
- uncontrolled diabetes
- history or concomitant presence of any other malignancy, except for:
non-melanoma skin cancer, carcinoma in situ of the cervix, any other
effectively treated malignancy that has been in remission for >5 years or that
is highly likely to be cured at time of enrollment.
- pregnant or breast feeding
- no informed consent
- participation in other (interventional) clinical trials without permission of
the study team.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL81867.029.22 |