Circulating Tumor DNA Genotyping for Biological Monitoring of Patients Treated in the FIL-Rouge Clinical Trial (FIL-RougeBIO)

December 30, 2024 updated by: Fondazione Italiana Linfomi - ETS

Circulating Tumor DNA Genotyping for Biological Monitoring of Patients with Advanced-stage Classical HL Receiving Upfront ABVD-based Chemotherapy. an Ancillary Study to the FIL-Rouge Phase III Trial

Prospective, multicenter, non-interventional, biological study ancillary to FIL-Rouge clinical trial (NCT03159897) enrolling patients affected by Advanced-stage Hodgkin Lymphoma, ABVD-based upfront treatment in 19 centers in Italy part of Fondazione Italiana Linfomi.

Study Overview

Status

Completed

Conditions

Detailed Description

The FIL-Rouge design provides an ideal environment for validating the liquid biopsy in Classical Hodgkin lymphoma (cHL), since one arm of the study will utilize a PET/CT-adapted strategy (Positron Emission Tomography/Computed Tomography)for treatment, while the second arm will be devoid of any PET/CT-adaptation of therapy. Also, estimating prospectively differences in residual disease between the two study arms of the FIL-Rouge will provide an important biologic tool to validate the concept of dose-intensification within the ABVD therapeutic platform.

This study aims at the prospective validation of the concept of the liquid biopsy as a biomarker for disease response assessment in cHL. The patients enrolled in the FIL-Rouge clinical trial at the centers participating in this study and consenting to the biological study FIL-RougeBIO will be considered for this study. After providing written informed consent, relevant patients will be evaluated for detecting cancer gene mutations in ctDNA (Circulating Tumor DNA) for measuring residual disease. All clinical data useful for data analyses of this study will derive from the FIL-Rouge clinical trial.

Given the non-interventional design of the study, project participants will not have immediate potential benefits.The enrollment in FIL-RougeBIO will parallel the original protocol until reaching the 500 programmed patients. The results of this study could benefit future patients with the same condition.

Study Type

Observational

Enrollment (Actual)

100

Contacts and Locations

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

Study Locations

  • Italy
      • Avellino, Italy
        • Azienda Ospedaliera S.Giuseppe Moscati - S.C. Ematologia e Trapianto emopoietico
      • Bari, Italy
        • IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia
      • Brescia, Italy
        • ASST Spedali Civili di Brescia - Ematologia
      • Milano, Italy
        • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
      • Napoli, Italy
        • Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - UOC Ematologia Oncologica
      • Pagani, Italy
        • Presidio ospedaliero "A. TORTORA" - U.O. Onco-ematologia
      • Palermo, Italy
        • A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
      • Pavia, Italy
        • IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
      • Perugia, Italy
        • Ospedale S. Maria della Misericordia - Ematologia
      • Pescara, Italy
        • P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
      • Rimini, Italy
        • Ospedale degli Infermi di Rimini - U.O. di Ematologia
      • Rozzano, Italy
        • Istituto Clinico Humanitas - U.O. Ematologia
      • Torino, Italy
        • A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia

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

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Eligibility criteria for participation in this study require:

  • Enrollment in the FIL-Rouge clinical trial;
  • Evidence of signed informed consent for the biological FIL-RougeBIO study.

Description

Inclusion Criteria: FIL ROUGE INCLUSION CRITERIA

  • Histologically confirmed classical HL
  • Previously untreated disease
  • Age 18-60 years
  • Ann Arbor stage IIB with extranodal involvement and/or bulk, III and IV
  • At least one target PET-avid bidimensionally assessable lesion
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2

  • Adequate organ and marrow function as defined below:

    • Absolute neutrophil count >1,0 x109/L, platelets >75 x109/L
    • Total bilirubin <2 mg/dl without a pattern consistent with Gilbert's syndrome
    • Aspartate Transaminase and Alanine Transaminase (AST/ALT) <3 X institutional Upper Limits of Normality (ULN)
    • Creatinine within normal institutional limits or creatinine clearance >50 mL/min/1.73 m2
  • Females of childbearing must have a negative pregnancy test under medical supervision even if patients had been using effective contraception
  • Life expectancy > 6 months
  • Able to adhere to the study visit schedule and other protocol requirements
  • Signed (or legally acceptable representatives must sign) informed consent indicating that patients understand the purpose of and procedures required for the study and are willing to participate in the study.
  • Access to PET-CT (Positron Emission Tomography/Computed Tomography) scans facilities qualified by FIL

Exclusion Criteria: FIL ROUGE EXCLUSION CRITERIA

  • Nodular Lymphocyte Predominant HL
  • Ann Arbor stage IIB without extranodal involvement and/or mediastinal bulky
  • Prior chemotherapy or radiation therapy
  • Pregnant or lactating females
  • Known hypertension, cardiac arrhythmia, conduction abnormalities, ischemic cardiopathy, left ventricular hypertrophy or left ventricular ejection fraction (LVEF) ≤50% at echocardiography.
  • Abnormal QTc interval prolonged (>450 msec in males; >470 msec in women)
  • Diffusion lung capacity for CO (DLCO)and/or Forced expiratory volume in the 1st second (FEV1) tests <50% of predicted not due to mediastinal compression or parenchymal lymphoma
  • Known cerebral or meningeal disease (HL or any other etiology)
  • Prior history of malignancies unless the patient has been free of the disease for five years. Exceptions include the following: basal cells carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast and prostate cancer with the TNM stage of T1a or T1b
  • Uncontrolled infectious disease
  • Human immunodeficiency virus (HIV) positivity or active infectious A, B or C hepatitis. HBsAg-negative patients with anti-HBc (Hepatitis B core) antibody and can be enrolled provided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatment with nucleos(t)ide analogs is provided (Lamivudine)
  • Uncompensated diabetes
  • Refusal of adequate contraception
  • Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Advanced-stage Hodgkin Lymphoma patients (1)
All patients will be accrued by investigators from the 19 best recruiting centers in the FIL-Rouge clinical trial. Patients had undergone to ABVD-based upfront treatment in FIL-Rouge trial (Comparator arm).
Advanced-stage Hodgkin Lymphoma patients (2)
All patients will be accrued by investigators from the 19 best recruiting centers in the FIL-Rouge clinical trial. Patients had undergone to ABVD-based upfront treatment in FIL-Rouge trial (Experimental arm).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate (CRR)
Time Frame: The endpoint will be assessed from the beginning of the study up to 76 months
Complete Response Rate (CRR) is defined as the proportion of patients achieving a Complete Remission (CR) at the end of treatment;
The endpoint will be assessed from the beginning of the study up to 76 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of Circulating tumor DNA (ctDNA) analysis versus interim PET/CT (Positron Emission Tomography/Computed Tomography)
Time Frame: The endpoint will be assessed from the beginning of the study up to 76 months
Diagnostic accuracy of Circulating tumor DNA (ctDNA) analysis versus interim PET/CT (sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios accuracy); The endpoint will be evaluated through specific timepoints.
The endpoint will be assessed from the beginning of the study up to 76 months
Progression Free Survival (PFS) with at least three years of follow up
Time Frame: The endpoint will be assessed from the beginning of the study up to 76 months
PFS is defined as the interval elapsing from randomization until lymphoma progression/relapse or death as a result of any cause.
The endpoint will be assessed from the beginning of the study up to 76 months

Collaborators and Investigators

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

Sponsor

Fondazione Italiana Linfomi - ETS

Investigators

  • Principal Investigator: Antonio Pinto, MD, Dipartimento di Ematologia, Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, Napoli, Italy

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)

April 8, 2020

Primary Completion (Actual)

November 2, 2021

Study Completion (Actual)

November 3, 2024

Study Registration Dates

First Submitted

September 6, 2021

First Submitted That Met QC Criteria

September 24, 2021

First Posted (Actual)

October 4, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 30, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL-RougeBIO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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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