|- candidate number||28318|
|- NTR Number||NTR6876|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||11-dec-2017|
|- Secondary IDs||NL52872.078.15 |
|- Public Title||Hodgkin-biomarkers
|- Scientific Title||Identification of pediatric Hodgkin lymphoma biomarkers and novel therapeutic targets|
|- hypothesis||Although classical Hodgkin Lymphoma (CHL) in pediatric patients has a good prognosis, the outcome is associated with a substantial proportion of treatment-related toxicity and still about 10-20% of the patients progress during or relapse after treatment. Strikingly, therapeutic regimens have not changed much during the past decades. Current treatment protocols rely on chemo- and radiotherapy, whereby patients are classified at diagnosis into three different treatment groups based on a clinical staging system. Radiotherapy can be omitted based on Fluoro-Deoxyglucose-Positron emission tomography CT (PET-CT) treatment response. |
HL is considered an immunological disease, where reactive cells in the tumor microenvironment greatly outnumber malignant Hodgkin- and Reed-Sternberg (HRS) cells. The microenvironment supports proliferation and survival of HRS cells. Due to active crosstalk between HRS cells and their microenvironment, serum biomarkers should be detectable and may be a surrogate for lymphoma viability. HL biology impedes development of in vitro and in vivo assays for functional studies to discover new therapeutics. Genetic analysis of malignant Hodgkin cells has been hampered by their scarcity and has largely been done with laser-dissected samples. In addition, apart from a clinical staging system at diagnosis, there have been no prognostic molecular markers to stratify patients into different therapy groups. Taken together this calls for efforts to identify biomarkers and get an in-depth understanding of HL immunology and biology to discover new therapeutic targets en less toxic therapies.
|- Healt Condition(s) or Problem(s) studied||Pediatric Hodgkin lymphoma |
|- Inclusion criteria||In order to be eligible to participate in this study, a subject must meet all of the following criteria:|
• Diagnosis of classical Hodgkin Lymphoma confirmed by reference pathology
• Patient aged below 18 at time of diagnosis
• Treatment according the European Network of Paediatric Hodgkin`s Lymphoma Second International Inter-Group Study for Classical Hodgkin’s Lymphoma in Children and Adolescents (EuroNet-PHL-C2) protocol.
• Written informed consent of the patient and/or the patient's parents or guardians according to national laws
|- Exclusion criteria||A potential subject who meets any of the following criteria will be excluded from participation in this study:|
• HIV positivity
• Other underlying immunologic disorders causing an inadequate or overactive immune response, with the exception of Epstein Barr Virus
|- mec approval received||yes|
|- multicenter trial||yes|
|- planned startdate ||16-nov-2016|
|- planned closingdate||31-dec-2020|
|- Target number of participants||300|
|- Interventions||Not applicable,|
|- Primary outcome||The aim of this project is to identify biomarkers and novel therapeutic targets for pediatric Hodgkin lymphoma. |
|- Secondary outcome||To achieve this aim we defined three objectives:|
1.Hodgkin Reed-Sternberg cells: To perform whole exome sequencing and gene expression arrays of FACS-sorted malignant Hodgkin and Reed-Sternberg cells. To get insights in the genetic profile of HRS cells and possibly translate this into future therapeutic targets.
2. Tissue microenvironment: To investigate the tumor microenvironment by immunohistochemistry and gene expression profiling of microenvironment-derived T-cells.
Hereby identification and validation of new markers (TARC, PD-1). This will possibly translate into novel therapeutic targets, for example PD-1–blocking antibody.
3. Serum biomarkers: To investigate the value of serum TARC and other biomarkers (see table 1 of the protocol) and cell-free DNA (cfDNA) as disease response markers after each cycle of chemotherapy and directly compare it to PET-scans, which is used for response assessment in the current protocol. Analysing of serum and blood samples after treatment and during follow-up to investigate its value as markers for disease recurrence.
|- Timepoints||Baseline characteristics |
Clinical parameters including age, sex, stages according to the Cotswolds revision of the Ann Arbor staging system, histology and the presence of B symptoms will be collected. The following laboratory parameters will be recorded at time of diagnosis and during follow-up at the same time points as serum and blood samples for biomarker identification are taken: Erythrocyte sedimentation rate (ESR), leukocyte count and differentiation, lymphocyte subpopulations, thrombocyte count, hemoglobin, creatinine, albumin and C-reactive protein. EBV status and treatment regime will be registered at diagnosis.
Serial serum and blood samples will be collected at diagnosis (baseline) and at fixed time points during treatment and follow-up
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||dr. A. Beishuizen|
|- CONTACT for SCIENTIFIC QUERIES||dr. A. Beishuizen|
|- Sponsor/Initiator ||Erasmus Medical Center, Sophia Children's Hospital|
(Source(s) of Monetary or Material Support)
|Erasmus Medical Center, Sophia Children's Hospital|
|- Brief summary|
|- Main changes (audit trail)||Summary of changes compared to previous version |
· Addition of the analysis of cell-free circulating tumor DNA (ctDNA) in the peripheral blood.
· Timepoints for blood samples are changed for all groups.
· More blood samples are collected.
|- RECORD||11-dec-2017 - 27-dec-2017|