Prognostic Significance of ctDNA in HL

Interni hematologicka klinika FNKV

Status: Enrolling

Conditions: Prognostic Cancer Model

Study type: Observational

Funder types: Other; NETWORK

Identifiers

NCT06263530

NU22-03-00182

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

500 participants in 6 patient groups

Standard first line treatment, stages I or II without risk factors

Description:

Standard first-line treatment that includes 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and involved site radiotherapy of 20 Gy in early clinical stages I or II without risk factors.

Patients < 60 years, stages I or II and 1 risk factor

Description:

Patients below 60 years in intermediate clinical stages I or II with at least one risk factor are treated with 2 cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) escalated and 2 cycles of ABVD in PET-4 negative cases. Involved site radiotherapy of 30 Gy is indicated in PET-4 positive patients with intermediate stages after chemotherapy.

Patients < 60 years, stages III or IV with MMT and/or EN disease

Description:

Patients in advanced stages III or IV and patients in stage IIB with massive mediastinal tumor and/or extranodal disease are treated with 4 or 6 cycles of BEACOPP escalated based on PET-2 negativity or positivity.

Elderly patients ≥ 60 years and 1 risk factor

Description:

Elderly patients in intermediate stages are treated with 2 cycles of ABVD and 2 cycles of AVD without bleomycin and involved site radiotherapy of 30 Gy.

Elderly patients ≥ 60 years, stages III or IV

Description:

Elderly patients in advanced stages are treated with 2 cycles of ABVD and 4 cycles of AVD without bleomycin

Relapsed patients up to 65 years

Description:

The treatment for patients in relapse up to the age of 65 years is two cycles of platinum based salvage chemotherapy: cisplatin, cytarabine and dexamethasone (DHAP) or ifosfamide, carboplatin, etoposide (ICE) followed by high- dose chemotherapy and autologous stem cell transplantation (ASCT).