Prognostic Significance of ctDNA in HL

Recruiting

• Conditions: Prognostic Cancer Model

• Registration Number: NCT06263530
• Lead Sponsor: Interni hematologicka klinika FNKV

Brief Summary

Specific somatic mutations using ctDNA will be analyzed in predefined subgroups of cHL (e.g., age \<60 and ≥ 60 years, EBV). These mutations will be correlated with response to the treatment in the first line, in the relapse, during brentuximab vedotin and/or nivolumab treatment. Circulating tumor DNA will be correlated with the extent of tumor mass and chemo/radiotherapy.

Detailed Description

Samples of plasma from peripheral blood will be taken for investigational ctDNA examination during the specific timepoints: at diagnosis, after 2 cycles of initial chemotherapy, at the end of chemotherapy, 3 months after radiotherapy, at the diagnosis of the first relapse, after salvage chemotherapy before ASCT, 3 months after ASCT, at the diagnosis of second relapse and every 3 months during brentuximab vedotin treatment or during nivolumab treatment until progression. The buccal swab for germline DNA extraction will be performed at the time of enrollment into the study. Samples of peripheral blood for EBV-DNA analysis will be obtained from the EBV-positive cHL patients to measure EBV load at the same time-points as ctDNA. Microdissected HRS cells from fresh frozen biopsies at the diagnosis and at the relapse will be used for tumor cells next generation sequencing.

Study Timeline

• Study Start: 2022-01-02
• Study First Submitted: 2023-11-14
• Primary Completion: 2023-12-31
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-08
• Last Update Submitted: 2024-02-08
• Study First Posted: 2024-02-16
• Last Update Posted: 2024-02-16
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patients ≥ 18 years with newly histologically confirmed classical Hodgkin lymphoma (cHL) will be enrolled
• signing the informed consent

Exclusion Criteria

• Pacients without signing the informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantitative analysis of ctDNA level during the first-line chemotherapy	4 years	Quantitative analysis of ctDNA level during the first-line chemotherapy: 1. analysis in relation to the type of chemotherapy: BEACOPP escalated vs ABVD; 2. dynamics of ctDNA decline in correlation with treatment response
Identification of tumor specific mutation profiles at relapse of classical HL	4 years	Identification of tumor specific mutation profiles at relapse of classical Hodgkin lymphoma: 1. detection of newly developed mutations in comparison to the initial diagnosis; 2. characteristics of mutations in HL tumors refractory to brentuximab vedotin; 3. characteristics of mutations in HL tumors refractory to nivolumab
Identification of tumor specific mutation profiles at dg. of HL based on ctDNA	4 years	Identification of tumor specific mutation profiles at diagnosis of classical Hodgkin: 1. age at diagnosis \< 60 years in comparison to patients with age at diagnosis 60 years and more; 2. EBV negative versus EBV positive cases; 3. correlation with the first line treatment outcome lymphoma based on ctDNA analysis with correlation to clinical and pathological characteristics

Secondary Outcome Measures

Name	Time	Method
In vitro functional characterization of identified DNA variants and/or mutations	4 years	In vitro functional characterization of identified DNA variants and/or mutations: 1. variants with unknown impact on classical HL development; 2. variants identified as associated with features analyzed in above mentioned goals

Trial Locations

Locations (5)

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, Czechia

University Hospital Olomouc; 🇨🇿 Olomouc, Czechia

University Hospital Kralovske Vinohrady; 🇨🇿 Praha, Czechia

Charles University; 🇨🇿 Praha, Czechia

General University Hospital; 🇨🇿 Praha, Czechia