Prognostic Significance of ctDNA in HL

NCT06263530 | Recruiting DMC

• 1 other identifier: NU22-03-00182
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 5

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.

Conditions

Prognostic Cancer Model

Keywords

Hodgkin lymphoma; circulating tumor DNA; next generation sequencing

Outcome Measures

Primary Outcomes (3)

• Identification of tumor specific mutation profiles at dg. of HL based on ctDNA

  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

  4 years

• Quantitative analysis of ctDNA level during the first-line chemotherapy

  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

  4 years

• Identification of tumor specific mutation profiles at relapse of classical HL

  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

  4 years

Secondary Outcomes (1)

• In vitro functional characterization of identified DNA variants and/or mutations

  4 years

Study Arms (6)

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

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

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

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

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

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

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).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Pacients without signing the informed consent

Sponsors & Collaborators

• Interni hematologicka klinika FNKV: lead
• Charles University, Czech Republic: collaborator
• General University Hospital, Prague: collaborator
• University Hospital Olomouc: collaborator
• University Hospital Hradec Kralove: collaborator
• University Hospital, Motol: collaborator

Study Sites (5)

University Hospital Hradec Kralove

Hradec Králové, 50005, Czechia

RECRUITING

University Hospital Olomouc

Olomouc, 77520, Czechia

RECRUITING

University Hospital Kralovske Vinohrady

Prague, 10034, Czechia

RECRUITING

Charles University

Prague, 12108, Czechia

ACTIVE NOT RECRUITING

General University Hospital

Prague, 12808, Czechia

RECRUITING

Related Publications (3)

• Dusek L, Majek O. Editorial. Klin Onkol. 2014;27 Suppl 2:3. No abstract available.

  PMID: 25629123 BACKGROUND

• 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.

  PMID: 25493581 BACKGROUND

• 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.

  PMID: 32050133 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Identification of tumor specific mutation profiles at diagnosis of classical Hodgkin lymphoma Quantitative analysis of ctDNA level during the first-line chemotherapy Identification of tumor specific mutation profiles at relapse of classical Hodgkin lymphoma In vitro functional characterization of identified DNA variants and/or mutations

MeSH Terms

Conditions

Hodgkin Disease

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Heidi Mocikova, M.D., Ph.D.

  Faculty Hospital Kralovske Vinohrady

  STUDY CHAIR

Central Study Contacts

Heidi Mocikova, M.D., Ph.D.

CONTACT

+420267163554; heidi.mocikova@fnkv.cz

Ondrej Havranek, assoc. prof.

CONTACT

+420325873029; ondrej.havranek@lf1.cuni.cz

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: February 16, 2024
• Study Start: January 2, 2022
• Primary Completion: December 31, 2023
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 16, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (5)