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

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05066555

Collaborator

(none)

100

Enrollment

Locations

33.8

Anticipated Duration (Months)

7.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma

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 Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 8, 2020

Anticipated Primary Completion Date :

Jan 31, 2023

Anticipated Study Completion Date :

Jan 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

Complete Response Rate (CRR) [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;

Secondary Outcome Measures

Diagnostic accuracy of Circulating tumor DNA (ctDNA) analysis versus interim PET/CT (Positron Emission Tomography/Computed Tomography) [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.
Progression Free Survival (PFS) with at least three years of follow up [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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