Changing Paragidms In The Prognostic Assessment Of Hodgkin Lymphoma (LH_BIO)

May 28, 2026 updated by: Azienda USL Reggio Emilia - IRCCS

Classical Hodgkin's Lymphoma (cHL) is a rare but highly treatable malignancy of the immune system, primarily affecting young adults. Despite significant therapeutic advancements, frontline treatment failure occurs in up to 30% of cases, with relapse or refractory disease affecting over 50% of these patients. The main therapeutic challenge in cHL remains achieving an optimal balance between disease control and reducing long-term adverse effects. Current prognostic tools only partially capture patient heterogeneity, and cHL continues to evolve spatially and temporally throughout the course of the disease. Personalized treatment strategies require novel integrated tools that better monitor tumor complexity and anticipate disease progression.

Fluorodeoxyglucose positron emission tomography (FDG-PET) has improved risk stratification in cHL, as metabolic response during or after chemotherapy strongly correlates with disease progression and survival. However, FDG-PET has limitations, including the absence of standardized criteria and the necessity to initiate treatment before response assessment. To overcome these limitations, molecular profiling and radiomic analysis of baseline FDG-PET data may provide deeper insights into tumor biology, improving prognostic accuracy.

This observational study aims to dissect the genetic and phenotypic heterogeneity of cHL at diagnosis and during disease evolution, with the goal of identifying novel prognostic biomarkers. These findings could lead to better treatment personalization, increasing cure rates while minimizing treatment-related toxicity. The study is based on the hypothesis that correlating DNA profiling at diagnosis, gene expression, and radiomic features may enable the identification of high-risk signatures, refining prognostic models in cHL. Additionally, liquid biopsy represents a non-invasive method for assessing tumor mutational complexity. The analysis of circulating DNA (cDNA) throughout disease progression could provide insights into genetic evolution and help predict overt progression before clinical manifestations occur.

The primary objective is to define the genetic mutational profile of cHL at disease progression. As secondary objectives, it will evaluate whether liquid biopsy can accurately recapitulate the genetic heterogeneity observed in tumor tissue, determine the predictive accuracy of liquid biopsy in anticipating disease progression, and correlate genomic and radiomic features with patient outcomes to refine risk stratification and therapeutic decision-making.

By integrating molecular and imaging-based biomarkers, this study aims to enhance personalized treatment strategies, improve risk-adapted therapeutic approaches, and ultimately optimize curability and quality of life for patients with cHL.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This study has both retrospective and prospective components. The prospective part includes patients with Classical Hodgkin's Lymphoma (cHL) who have completed active treatment and entered follow-up (Cohort A), as well as patients with a histological confirmation of relapse or progression (Cohort B). The retrospective cohort (Cohort C) consists of 235 consecutive cHL patients collected from the archives of the Hematology Unit of AUSL-IRCCS between 2004 and 2019, along with up to 250 cHL patients diagnosed between 2016 and 2021 from other Italian hematology centers.

Study Type

Observational

Enrollment (Estimated)

755

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 Locations

  • Italy
      • Avellino, Italy
        • Recruiting
        • A.O.S.G. Moscati
        • Contact:
        • Principal Investigator:
          • Sonya De Lorenzo, MD
      • Brescia, Italy
      • Padova, Italy
        • Recruiting
        • Istituto Oncologico Veneto
        • Contact:
        • Principal Investigator:
          • Dario Marino, MD
      • Palermo, Italy
        • Recruiting
        • Azienda Ospedaliera "Ospedali Riuniti Villa Sofia-Cervello"
        • Contact:
        • Principal Investigator:
          • Caterina Patti, MD
      • Perugia, Italy
      • Perugia, Italy
        • Recruiting
        • Ospedale S. Maria della Misericordia, Azienda Ospedaliera di Perugia
        • Contact:
          • Eleonora Lusenti, Clinical Research Coordinator
          • Phone Number: eleo95@gmail.com
        • Principal Investigator:
          • Gaetano Vaudo, MD
      • Piacenza, Italy
        • Recruiting
        • AUSL Piacenza
        • Principal Investigator:
          • Annalisa Arcari, MD
        • Contact:
      • Terni, Italy, 05100
        • Recruiting
        • Azienda Ospedaliera Santa Maria - Terni
      • Torino, Italy
        • Recruiting
        • AOU Città della Salute e della Scienza
        • Principal Investigator:
          • Barbara Botto, MD
        • Contact:
      • Torino, Italy
        • Recruiting
        • AOU Città della salute e della Scienza, "Le Molinette"
        • Contact:
        • Principal Investigator:
          • candida Vitale, MD
    • MI
      • Milan, MI, Italy, 20162
        • Recruiting
        • ASST Grande Ospedale Metropolitano Niguarda
        • Principal Investigator:
          • Vittorio Ruggero Zilioli, MD
        • Contact:
    • RE
      • Reggio Emilia, RE, Italy, 42123
        • Recruiting
        • Azienda USL IRCCS Di Reggio Emilia
        • Principal Investigator:
          • Stefano Luminari, MD
        • 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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study will involve three patient cohorts, with participants recruited from multiple centers across Italy during routine follow-up visits.

Cohort A will include 70 patients with classical Hodgkin lymphoma (cHL) who have a histological confirmation of relapse or progression. These patients will be enrolled at the time of disease relapse/progression, and plasma samples for ctDNA analysis will be collected concurrently.

Cohort B will consist of 200 cHL patients who have completed active treatment and entered the follow-up phase. Plasma samples will be collected from these patients at the time of enrollment (P0) and again at a six-month follow-up (P6FU). This cohort will be followed for a minimum of two years from the time of enrollment.

Cohort C is a retrospective cohort that will be divided into two subgroups:

Training cohort: 235 consecutive cHL patients collected from the archives of the Hematology Unit of AUSL-IRCCS between 2004 and 2019. This cohort is representative of the ge

Description

Inclusion Criteria:

  • Age >18 anni
  • Written informed consent signed

Cohort A

  • Age >18 years
  • Histologically confirmed diagnosis of relapsed/refractory classical Hodgkin lymphoma identified during induction or follow-up
  • Available formalin-fixed, paraffin-embedded (FFPE) biopsy at diagnosis and at the time of progression/relapse
  • Available plasma sample at progression (before the beginning of salvage therapy)
  • Available FDG-PET evaluation at study enrollment
  • Available clinical, laboratory, and radiologic data at diagnosis and relapse

Cohort B

  • Diagnosis of classical Hodgkin lymphoma
  • Completion of first-line standard systemic treatment (chemotherapy-based or chemoradiotherapy combined modality)
  • Available plasma sample at the end of treatment (at least 30 days from the last chemotherapy)
  • Available FFPE biopsy at diagnosis
  • No further treatment planned
  • Available clinical, laboratory, and radiologic data at diagnosis and response evaluation
  • Patient's willingness to undergo 6 months follow-up plasma sample collection and to attend regular follow-up

Cohort C

  • Histologically confirmed diagnosis of classical Hodgkin lymphoma
  • Standard treatment as per available guidelines (e.g., ESMO guidelines)
  • Available treatment data, response, and follow-up data
  • Available FFPE biopsy at diagnosis
  • Available FDG-PET evaluation at study enrollment

Exclusion Criteria:

  • Patients with nodular lymphocyte predominant Hodgkin lymphoma are not eligible; all other subtypes including nodular sclerosis, lymphocyte-depleted, lymphocyte-rich, and mixed cellularity Hodgkin lymphoma may be enrolled.
  • Active HIV, HBV, HCV viral infection
  • Concomitant neoplasm not treated with a curative aim

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
Post-Treatment Follow-Up Cohort (Cohort A)
cHL patients who have completed active treatment and entered follow-up.
Relapsed/Progressive Disease Cohort (Cohort B)
cHL patients with a histological confirmation of relapse or disease progression.
Retrospective cHL Cohort (Cohort C)
Consecutive cHL patients from the archives of the Hematology Unit of AUSL-IRCCS, diagnosed between 2004 and 2019 and 250 cHL patients diagnosed between 2016 and 2021 from other Italian hematology centers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic Mutational Profiling of cHL at Progression
Time Frame: At enrollement
The mutational profile of Classical Hodgkin's Lymphoma patients enrolled in Cohort A will be generated using deep sequencing technologies, including Cancer Personalized Profiling by deep-sequencing (CAPP-seq), on biopsy samples collected at the time of initial diagnosis and at the time of progression to identify key alterations associated with disease progression and aggressiveness.
At enrollement

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liquid Biopsy Ability to Recapitulate Tissue Genetic Heterogeneity
Time Frame: Up to 4 years
Circulating tumor DNA (ctDNA) from plasma samples collected at baseline (Cohort B) and at the time of disease progression (Cohorts A and B) will be analyzed using CAPP-seq and compared with matched germline DNA (gDNA). Identified mutations will be compared to a background variant database to filter out technical sequencing errors and identify true positive alterations. Heatmaps and COSMIC database annotations will be used to assess the functional relevance of selected variants. The mutational profile in plasma will be compared with biopsy results obtained at progression to evaluate the ability of ctDNA to capture tumor heterogeneity and progression-related alterations.
Up to 4 years
Accuracy of Liquid Biopsy in Anticipating Disease Progression
Time Frame: From 2 up to 4 years
Plasma samples of Cohort B patients will be collected at enrollement and at 6 months of follow-up, and the presence of mutations will be assessed using deep sequencing (CAPP-seq). The results will be compared with clinical outcomes over a follow-up period of at least 2 years to determine the specificity and sensitivity of liquid biopsy in predicting progression.
From 2 up to 4 years
Correlation between Gene Expression Profiling and Progression-free survival (PFS)
Time Frame: Up to 4 years
Gene expression profiling conducted on tissue samples from subjects in Cohort C at diagnosis will be correlated with progression-free survival (PFS).
Up to 4 years
Correlation between Gene Expression Profiling and cnical events like relapse and refractoriness
Time Frame: Up to 4 years
Gene expression profiling conducted on tissue samples from subjects in Cohort C at diagnosis will be correlated with cnical events like relapse and refractoriness).
Up to 4 years

Collaborators and Investigators

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

Sponsor

Azienda USL Reggio Emilia - IRCCS

Investigators

  • Principal Investigator: Luminari Stefano, MD, Azienda USL - IRCCS di Reggio Emilia

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)

June 23, 2022

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 7, 2025

First Submitted That Met QC Criteria

February 7, 2025

First Posted (Actual)

February 12, 2025

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 696/2021/TESS/IRCCSRE

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

product manufactured in and exported from the U.S.

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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