Brain tumors: Characterize and quantify changes in immune parameters during disease in patients with a CNS malignancyAML: Characterize and quantify changes in immune parameters and immunotherapeutic targets during disease in pediatric patients with…
ID
Source
Brief title
Condition
- Leukaemias
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Brain tumors: To characterize and quantify changes in immune parameters during
disease within patients with a CNS malignancy
AML: To characterize and quantify changes in immune parameters during disease
within patients with AML.
Secondary outcome
Brain tumors:
Secondary Objectives
To evaluate the effect of therapy on the immune profiles
To evaluate survival for different molecular- and immune profiles
Explorative Objectives
To determine tumor-specific cell surface proteins
To characterize tumor infiltrating lymphocytes
To determine faeces composition
To correlate molecular characteristics with the immune profile for the
different tumor entities
AML:
Exploratory objectives:
To evaluate survival and treatment response for different molecular- and immune
profiles
To characterize the amenability of primary AML samples and immune cells to
respond to immunotherapy in preclinical models
Background summary
Brain tumors: Survival amongst children with high-grade CNS tumors is dismal.
Survival of low-grade tumors comes with severe morbidity New treatment
modalities are needed to increase survival and diminish morbidity. Immune
therapies like CAR-T therapy, checkpoint inhibition and oncolytic viruses are
new and promising options that need to be explored for this population. In
order to implement smart intervention trials for immune therapy,
characterisation of the immune system/response in children with CNS tumors is
crucial. Currently this information is hardly available. With this study we aim
to obtain a broad spectrum of immunological parameters from the different body
compartments including the tumor (and its microenvironment), bone marrow, feces
CSF and blood.
AML: Although therapy regimens consisting of intensive chemotherapy,
hematopoietic stem cell transplantation and optimized supportive care have
approached cure rates of 70% for children with AML, outcomes for children with
refractory or relapsed disease remain poor and highlight the need for
alternative treatment approaches. Immune therapies like CAR-T cell therapy,
checkpoint inhibition and bispecific antibodies are new and promising options
that need to be explored for this population. In order to implement
intervention trials for immune therapy, characterisation of the immune
system/response in children with AML is crucial. Currently this information is
hardly available. With this study we aim to obtain a broad spectrum of
immunological parameters and targets at various time points during the
treatment process from different body compartments including the bone, bone
marrow and blood. These immunological profiles and their prognostic relevance
will then be used to guide hypotheses on which patients are most likely to
benefit from which immunotherapeutic intervention at which time point during
treatment.
Study objective
Brain tumors: Characterize and quantify changes in immune parameters during
disease in patients with a CNS malignancy
AML: Characterize and quantify changes in immune parameters and
immunotherapeutic targets during disease in pediatric patients with AML
Study design
Brain tumors: This is a prospective observational longitudinal cohort pilot
study, conducted in patients with newly diagnosed or relapsed brain tumors in
the Princess Maxima Center. Biopsy material, cerebrospinal fluid, peripheral
blood (cellular compartment and plasma), feces and bone marrow will be
collected at various time points
AML: This is a prospective observational longitudinal cohort pilot study,
conducted in patients with newly diagnosed or relapsed AML in the Princess
Maxima Center. Bone biopsy material, bone marrow aspirate and peripheral blood
will be collected at various time points.
Study burden and risks
Brian tumors: Bone marrow is no standard of care procedure for children with
paediatric brain tumors. This will only be performed during moments of general
anaesthesia in the context of standard of care, and is optional. A bone marrow
aspiration is usually painful for around 24 hours. Optimal pain medication will
be prescribed to minimize the burden. The burden for participating patients is
limited in comparison to other interventions during treatment. Analysis of the
bone marrow compartment is of utmost importance to understand and monitor the
impact of the immune system during (high grade) brain tumors. Without an
alternative method to gather these data, the impact for patients is in line
with the potential benefit.
AML: Bone biopsies during treatment (before second and third course of
chemotherapy for newly diagnosed patients and once after completion of
allo-SCT) are not standard of care procedure for children with pediatric AML,
while bone biopsies at diagnosis and relapse presentation are standard of care.
Bone biopsies will be performed during moments of general anaesthesia in the
context of standard of care bone marrow aspirate acquisition. Bone biopsy is
usually painful for around 24 hours. Optimal pain medication will be prescribed
to minimize the burden. The burden for participating patients is limited in
comparison to other interventions during treatment. Analysis of the spatial
tumor-immune interaction in bone biopsies is of utmost importance to understand
and monitor the reciprocal impact of AML cells on immune cells. The latter
cannot be retrieved with standard bone marrow aspirates as the spatial location
of cells is lost with this approach. Without an alternative method to gather
these data, we argue that the impact for patients is in line with the potential
benefit.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
For Brain tumor arm:
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
Patients
- Age 0 - 25 years at inclusion
- Newly diagnosed brain tumor or relapse of a brain tumor including
craniopharyngiomas
- MRI representing an image of a brain tumor, not resembling a germcell tumor
- Clinical indication for tumor biopsy/resection
- Written (parental) informed consent
Healthy controls
- Sibling of a patient already participating in the MIMIC brain study
- Age 0 - 25 years at inclusion
- Written (parental) informed consent
For AML:
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Age 0 - 21 years at inclusion
- Treatment at a Pediatric Cancer Center
- Newly diagnosed AML or relapse of AML
- Written (parental) informed consent
Exclusion criteria
For Brain tumor arm:
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Suspected germ cell tumor on radiology or based on tumor markers (αFP, βHCG)
For AML arm:
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- acute myeloid leukemia in children with Down syndrome
- acute promyelocytic leukemia (APL)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL75515.041.21 |
| Other | NL8967 |