The goal of this study is to improve risk stratification and treatment allocation for medium and high risk neuroblastoma patients by real time quantitative (RQ)- PCR-minimal residual disease (MRD) testing.We have recently developed a panel of RQ-PCR…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Determination of the value in high-risk neuroblastoma using RQ-PCR to test
the presence of PHOX2b, TH, DDC, DBH, GAP43 and CHRNA3. The BM samples will be
scored positive, negative or inconclusive and this outcome will be compared to
the conventional testing. The MRD status will be monitored at different time
points during treatment in BM and PB. The RQ-PCR data will be correlated to
survival data. Primary outcomes will be overall durvival (death) and event free
survival (relapse)
2. Paired BM and PB samples will be tested, scored (positive, negative and
inconclusive) and compared. This study will evaluate the effectiveness of
determining MRD in PB samples.
Secondary outcome
1. A secondary outcome is the clinical significance of MRD positive BM or PB
samples (using RQ-PCR) in non-high risk neuroblastoma patients. The BM or PB
samples will be scored positive, negative and inconclusive and this outcome
will be correlated to the event free or overall survival.
2. Furthermore we will use RQ-PCR testing with our set of markers to monitor
the MRD status after completing therapy. The PB samples will be scored
positive, negative or inconclusive and outcome will be correlated to the event
free or overall survival.
Background summary
Despite careful stratification and the development of multi-modality therapy
schemes, the prognosis of high-risk neuroblastoma is still about 30-40% and it
is not possible to predict which of these high risk patients succumb or will
survive. For the medium risk group the overall prognosis is about 70% with less
intensive treatment. On the one hand it is vital to improve our ability to
detect high risk patients in the medium risk group so they can be treated
accordingly. For the high risk group we want to identify the high risk patient
more likely to benefit from intensive treatment.
Study objective
The goal of this study is to improve risk stratification and treatment
allocation for medium and high risk neuroblastoma patients by real time
quantitative (RQ)- PCR-minimal residual disease (MRD) testing.
We have recently developed a panel of RQ-PCR targets for MRD detection in
neuroblastoma, some of them show no expression in normal bone marrow (BM) or
peripheral blood cells (PB). In contrast to this we know that the currently
used marker tyrosine hydroxylase (TH) and GD2-synthase show illegitimate
expression in surrounding hematopoietic tissues and can show clonal tumour
heterogeneity.
Study design
In a retrospective study we will test the expression of the markers on primary
tumour and on bone marrow (BM) samples of approximately 100 medium and high
risk patients at diagnosis and during treatment, as available from Dutch
patients at Sanquin, Amsterdam. We will further perform a prospective MRD study
using samples from Dutch and German high risk neuroblastoma patients. We will
investigate if MRD monitoring can improve BM staging at diagnosis, if MRD
monitoring at different time points can predict survival in high risk patients,
if MRD monitoring after completing therapy can predict early relapse and if MRD
monitoring in PB can add information compared to BM.
Study burden and risks
Extra peripheral blood (PB) (3-5 ml) and extra bone marrow (BM) (2 ml) will be
drawn during regular PB and BM punctions during and after therapy. Patients
will never get extra PB or BM punctions. Thereby there will not be an
additional risk associated with participation to this study. Patients will not
benefit of this study.
Meidreef 9
1105 AZ Amsterdam
NL
Meidreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
- children with high or medium risk neuroblastoma
- treated according to dutch-german protocol
Exclusion criteria
- children with low risk neuroblastoma
- children with ganglioneuroma
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 | NL18096.018.07 |