Identification of paediatric Hodgkin lymphoma biomarkers and novel therapeutic targets.

Identification of paediatric Hodgkin lymphoma biomarkers and novel therapeutic targets. - Hodgkin-biomarkers

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON54726

Enrollment

230

Registered

2016-07-21

Start date

2016-11-16

Completion date

Unknown

Last updated

2026-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hodgkin disease Hodgkin lymphoma malignant lymphoma

Interventions

None listed

Eligibility

Age

2 Years to 17 Years

Inclusion criteria

Inclusion criteria: In order to be eligible to participate in the Hodgkin lymphoma group, 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 or treatment for relapsed or refractory patients or according to the Open-label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults with Newly Diagnosed Classical Hodgkin Lymphoma with Inadequate (Slow Early) Response to Frontline Chemotherapy. • Written informed consent of the patient and/or the patient's parents or guardians according to national laws

Exclusion criteria

Exclusion criteria: - HIV positivity - Other underlying immunologic disorders causing an inadequate or overactive immune response, with the exception of Epstein Barr Virus

Design outcomes

Primary

Measure	Time frame
1. Genetic analysis of HRS cells By whole exome sequencing genetic alterations in malignant HRS cells will be discoverd. The changes of genomic material will be investigated and associated with existing oncogenes. The role of the genetic alterations for example in antigen presentation, chromosome integrity, transcriptional regulation and ubiquitination will be specified. If there are genes frequently mutated in the HRS cells, the role of these genes will be further explored. Genomic alterations will be correlated with therapy to response. 2. Tissue microenvironment Tissue samples will be examined to confirm expression of PD-1/PD-L1 and TARC by Hodgkin tumor cells. T-cell subpopulations, NK-cells, macrophages and immune inhibitory cytokines such as IL1-10 and TGF will be examined on tissue samples. These laboratory finding will be correlated with clinical course and outcome. 3. Blood biomarkers Levels of several serum proteins and cfDNA will be evaluated in HL patients and will be compared to controls to identify new biomarkers. These biomarkers will be correlated to staging, histology, presence of B symptoms, laboratory parameters and metabolic volume on FDG-PET. The value of TARC will be investigated as diagnostic marker for pediatric HL. Therefore, we will determine normal values of TARC pediatric patients without HL. We will investigate the sensitivity and specificity of TARC as a diagnostic biomarker in patients with pediatric HL. Second, the value of TARC as a disease response markers will be investigated by comparing it with FDG_PET scans during treatment. Finally TARC will be analyzed after treatment and during follow-up to investigate its value as markers for disease recurrence. If feasible, joint modelling for longitudinal TARC data and time-to-recurrence data will be done in order to investigate how changes in TARC influence the occurrence of a recurrence. In addition, predicted individual-specific biomarker values and recurrenc	—

Measure

Time frame

1. Genetic analysis of HRS cells By whole exome sequencing genetic alterations in malignant HRS cells will be discoverd. The changes of genomic material will be investigated and associated with existing oncogenes. The role of the genetic alterations for example in antigen presentation, chromosome integrity, transcriptional regulation and ubiquitination will be specified. If there are genes frequently mutated in the HRS cells, the role of these genes will be further explored. Genomic alterations will be correlated with therapy to response. 2. Tissue microenvironment Tissue samples will be examined to confirm expression of PD-1/PD-L1 and TARC by Hodgkin tumor cells. T-cell subpopulations, NK-cells, macrophages and immune inhibitory cytokines such as IL1-10 and TGF will be examined on tissue samples. These laboratory finding will be correlated with clinical course and outcome. 3. Blood biomarkers Levels of several serum proteins and cfDNA will be evaluated in HL patients and will be compared to controls to identify new biomarkers. These biomarkers will be correlated to staging, histology, presence of B symptoms, laboratory parameters and metabolic volume on FDG-PET. The value of TARC will be investigated as diagnostic marker for pediatric HL. Therefore, we will determine normal values of TARC pediatric patients without HL. We will investigate the sensitivity and specificity of TARC as a diagnostic biomarker in patients with pediatric HL. Second, the value of TARC as a disease response markers will be investigated by comparing it with FDG_PET scans during treatment. Finally TARC will be analyzed after treatment and during follow-up to investigate its value as markers for disease recurrence. If feasible, joint modelling for longitudinal TARC data and time-to-recurrence data will be done in order to investigate how changes in TARC influence the occurrence of a recurrence. In addition, predicted individual-specific biomarker values and recurrenc

—

Secondary

Measure	Time frame
Not applicable.	—

Countries

Netherlands

Outcome results