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NCT Number: NCT06822855

Changing Paragidms In The Prognostic Assessment Of Hodgkin Lymphoma

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.

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Key information

Conditions

Classical Hodgkin Lymphoma Classical Hodgkin Lymphoma Recurrent Classical Hodgkin Lymphoma Refractory

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

ASST Grande Ospedale Metropolitano Niguarda, Milan, MI, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Attilio Gennaro, Clinical Research Coordinator

CONTACT

[email protected]

+39 0522 295175

Sponsors and collaborators

Lead sponsor

Azienda USL Reggio Emilia - IRCCS

Other Gov

Registry information

Acronym: LH_BIO

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Feb 12, 2025
Registry last updated
May 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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