Prognostic Significance of ctDNA in HL

February 8, 2024 updated by: Interni hematologicka klinika FNKV

Prognostic Significance of Circulating Tumor DNA in Hodgkin Lymphoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Czechia
      • Hradec Kralove, Czechia, 50005
        • Recruiting
        • University Hospital Hradec Kralove
        • Contact:
      • Olomouc, Czechia, 77520
        • Recruiting
        • University Hospital Olomouc
        • Contact:
          • Vit Prochazka, prof. M.D.
          • Phone Number: +420588 442 878
          • Email: prochazv@fnol.cz
      • Praha, Czechia, 10034
        • Recruiting
        • University Hospital Královské Vinohrady
        • Contact:
        • Contact:
      • Praha, Czechia, 12108
        • Active, not recruiting
        • Charles University
      • Praha, Czechia, 12808
        • Recruiting
        • General University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Identification of tumor specific mutation profiles at dg. of HL based on ctDNA
Time Frame: 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
4 years
Quantitative analysis of ctDNA level during the first-line chemotherapy
Time Frame: 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
4 years
Identification of tumor specific mutation profiles at relapse of classical HL
Time Frame: 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
4 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
In vitro functional characterization of identified DNA variants and/or mutations
Time Frame: 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
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Interni hematologicka klinika FNKV

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Charles University, Czech Republic
University Hospital Olomouc
General University Hospital, Prague
University Hospital Hradec Kralove
University Hospital, Motol

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Heidi Mocikova, M.D., Ph.D., Faculty Hospital Kralovske Vinohrady

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 2, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 16, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 16, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NU22-03-00182

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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