Clinical trial NCT06263530: Prognostic Significance of ctDNA in HL
Official title: Prognostic Significance of Circulating Tumor DNA in Hodgkin Lymphoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prognostic Cancer Model
Keywords: Hodgkin lymphoma
circulating tumor DNA
next generation sequencing
Lead sponsor: Interni hematologicka klinika FNKV
Sponsor class: NETWORK
Collaborators: name: Charles University, Czech Republic
name: General University Hospital, Prague
name: University Hospital Olomouc
name: University Hospital Hradec Kralove
name: University Hospital, Motol
First posted: 2024-02-16
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients ≥ 18 years with new HL, all patients will undergo standard diagnostic procedures and will be divided based by stages and risk factors. Patients below 60 years will be divided into 3 treatment risk groups and treated according to the standard recommendations explained as well as elderly patients (see study groups). Younger relapsed patients will be treated with salvage platinum-based chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). Relapses after ASCT in younger patients or after at least two lines of chemotherapy in elderly patients will be treated with brentuximab vedotin (up to 16 cycles) or nivolumab until progression.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of tumor specific mutation profiles at dg. of HL based on ctDNA
timeFrame: 4 years
measure: Quantitative analysis of ctDNA level during the first-line chemotherapy
timeFrame: 4 years
measure: Identification of tumor specific mutation profiles at relapse of classical HL
timeFrame: 4 years
Secondary outcomes:
measure: In vitro functional characterization of identified DNA variants and/or mutations
timeFrame: 4 years
Other outcomes:
Locations:
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Praha
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: Charles University
city: Praha
country: Czechia
facility: General University Hospital
Study officials:
affiliation: Faculty Hospital Kralovske Vinohrady
name: Heidi Mocikova, M.D., Ph.D.
role: STUDY_CHAIR
References:
citation: Dusek L, Majek O. Editorial. Klin Onkol. 2014;27 Suppl 2:3. No abstract available.
citation: Mocikova H, Sykorova A, Stepankova P, Markova J, Michalka J, Kral Z, Buresova L, Belada D. [Treatment and prognosis of relapsed or refractory Hodgkin lymphoma patients ineligible for stem cell transplantation]. Klin Onkol. 2014;27(6):424-8. doi: 10.14735/amko2014424. Czech.
citation: Sykorova A, Mocikova H, Lukasova M, Koren J, Stepankova P, Prochazka V, Belada D, Klaskova K, Gaherova L, Chroust K, Buresova L, Markova J; Czech Hodgkin's Lymphoma Study Group. Outcome of elderly patients with classical Hodgkin's lymphoma. Leuk Res. 2020 Mar;90:106311. doi: 10.1016/j.leukres.2020.106311. Epub 2020 Jan 24.