FIL Study on ABVD DD-DI as Upfront Therapy in HL.

NCT03159897 | Completed Phase 3 DMC

• 1 other identifier: FIL-Rouge
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 46

Brief Summary

The FIL-Rouge is a randomized, open-label, multicenter, phase III, 2-arm study. The primary objective is to compare efficacy and tolerability of the intensified variant 'dose-dense/dose-intense ABVD' (ABVD DD-DI) with an interim PET response-adapted ABVD program as upfront therapy in advanced-stage classical Hodgkin Lymphoma (HL).

Conditions

Hodgkin Lymphoma

Keywords

advanced stage (IIB-IV); ABVD DD-DI; PET

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the interval elapsing from randomization until lymphoma progression or death as a result of any cause.

  3 years

Secondary Outcomes (8)

• Complete remission rate (CR rate)

  2 months and 6 months

• PET/CT response rate

  after 2 months of chemotherapy

• Event Free Survival (EFS)

  3 years

• Disease free survival (DFS)

  3 years

• Overall survival (OS)

  3 years

Study Arms (2)

Comparator arm

EXPERIMENTAL

Patients will receive 2 courses of standard ABVD (ABVD-28, d1, d15, cycles of 28 days) and then proceed to interim PET/CT evaluation. Those with a PET-2-negative scan (score 1-3 on 5PS) will continue with additional 4 ABVD courses while those with a PET-2-positive (score 4-5) scan will be diverted towards an intensification phase with either escalated BEACOPP or HDT plus ASCR, according to the preference of the centre. Upon completion of treatment, patients will be categorized for response (Lugano2014) by comparing actual PET/CT imaging with baseline, whether 6 ABVD cycles or ABVDx2 + intensification phase with BEACOPP or HDT/ASCR. A salvage rescue program will be planned for patients with Stable (\<PR) or Progressive Disease. ISRT 30 Gy will be delivered to complete responders (5PS score 1-2-3) on the initial bulky site(s), to focal rests in case of CR scoring 3 on 5PS with a residual size ≥ 2.5 cm and to focal rests uptakes in the event of PR scoring 4 or 5, whichever is the size.

Drug: Doxorubicin; Drug: Bleomycin; Drug: Vinblastine; Drug: Dacarbazine

Experimental arm

EXPERIMENTAL

Dose-dense and dose-intense ABVD regimen (ABVD DD-DI: intercycle 21 days, d1, d11; doxorubicin 35 mg/m2 DD 1 and 11) is given in cycles 1 to 4 and dose-dense ABVD (ABVD DD: intercycle 21 days, D1 and D11; conventional doxorubicin dose, e.g. 25 mg/m2 DD 1 and 11) is given as cycles 5 and 6). The treatment is not PET-adapted, and only patients with no response or progressive disease at interim FDG-PET as defined by the Lugano Classification (e.g., score 4 or 5 on 5PS with no significant change or with increased uptake matched with baseline and/or new FDG-avid foci consistent with lymphoma) will be diverted to salvage therapy. ISRT 30 Gy will be delivered to responder patients (DS=3), on focal PET-positive rests with a residual size ≥ 2.5 cm and on patients in PR with uptake scoring 4 or 5, whichever is the size.

Drug: Doxorubicin; Drug: Bleomycin; Drug: Vinblastine; Drug: Dacarbazine

Interventions

Doxorubicin DRUG

Comparator arm: cycle 1-2 (and eventually 3-6): 25 mg/m2 i.v. days 1,15. Experimental arm: Cycles 1 to 4: 35 mg/m2 i.v. days 1,11. Cycles 5 and 6: 25 mg/m2 i.v. days 1,11.

Comparator arm; Experimental arm

Bleomycin DRUG

Bleomicina Comparator arm: cycle 1-2 (and eventually 3-6): 10,000 units/m2 i.v. days 1,15. Experimental arm: cycles 1 to 4: 10,000 units/m2 i.v. days 1,11. Cycles 5 and 6: 10,000 units/m2 i.v. days 1,11.

Comparator arm; Experimental arm

Vinblastine DRUG

Vinblastina Comparator arm: cycle 1-2 (and eventually 3-6): 6 mg/m2 i.v. days 1,15. Experimental arm: cycles 1 to 4: 6 mg/m2 i.v. days 1,11. Cycles 5 and 6: 6 mg/m2 i.v. days 1,11.

Comparator arm; Experimental arm

Dacarbazine DRUG

Dacarbazina Comparator arm: cycle 1-2 (and eventually 3-6): 375 mg/m2 i.v. days 1,15. Experimental arm: cycles 1 to 4: 375 mg/m2 i.v. days 1,11. Cycles 5 and 6: 375 mg/m2 i.v. days 1,11.

Comparator arm; Experimental arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Histologically confirmed classical HL
• Previously untreated disease
• Age 18-60 years
• Ann Arbor stage IIB with extranodal involvement and/or mediastinal bulk, III and IV (Appendix A)
• At least one target PET-avid bidimensionally assessable lesion
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 (Appendix B)
• 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/1.72 m2 (Appendix C)
• Females of childbearing must have a negative pregnancy test at medical supervision even if had been using effective contraception
• Life expectancy \> 6 months
• Able to adhere to the study visit schedule and other protocol requirements
• Sign (or their legally acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Access to PET-CT scans facilities qualified by FIL

You may not qualify if:

• 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 (as defined by the updated Guidelines \[76\]), 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 related to impaired respiratory capacity due to airway compression by mediastinal masses 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 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 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
• 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.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (46)

I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1

Padua, Padova, 35128, Italy

Location

Ospedale delle Croci - Ematologia

Ravenna, Ravenna, Italy

Location

A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia

Alessandria, Italy

Location

Università Politecnica delle Marche, Clinica di Ematologia

Ancona, Italy

Location

Ospedale C.e G. Mazzoni -U.O.C. di Ematologia

Ascoli Piceno, Italy

Location

Azienda Ospedaliera S.Giuseppe Moscati -S.C. Ematologia e Trapianto emopoietico

Avellino, Italy

Location

Centro Riferimento Oncologico - S.O.C. Oncologia Medica A

Aviano, Italy

Location

AOU Policlinico Consorziale - U.O. Ematologia con Trapianto

Bari, Italy

Location

IRCCS Istituto Tumori Giovanni Paolo II

Bari, Italy

Location

Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia

Barletta, Italy

Location

A.O. Spedali Civili di Brescia - Ematologia

Brescia, Italy

Location

Ospedale Antonio Perrino - Ematologia

Brindisi, Italy

Location

Fondazione del Piemonte per l'Oncologia - IRCCS - Ematologia

Candiolo, Italy

Location

AORN S.Anna e S. Sebastiano - Oncoematologia

Caserta, Italy

Location

Ospedale di Castelfranco Veneto - Ematologia

Castelfranco Veneto, Italy

Location

ASST Cremona - Ematologia e CRTO

Cremona, Italy

Location

Ospedali Riuniti del Canavese

Ivrea, Italy

Location

Ospedale Vito Fazzi - Ematologia

Lecce, Italy

Location

Ospedale Madonna delle Grazie - Ematologia

Matera, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia

Meldola, Italy

Location

Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia

Messina, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, Italy

Location

USLL13 - Dipartimento di Scienze Mediche UOC di Oncologia ed Ematologia Oncologica

Mirano, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena - Ematologia

Modena, Italy

Location

Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - Ematologia Oncologica

Napoli, Italy

Location

Presidio ospedaliero "A. TORTORA"

Pagani, Italy

Location

A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia

Palermo, Italy

Location

AOU di Parma - UO Ematologia e CTMO

Parma, Italy

Location

IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia

Pavia, Italy

Location

AO di Perugia - Ematologia

Perugia, Italy

Location

P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi

Pescara, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, Italy

Location

A.O.R. "San Carlo" - U.O. Ematologia

Potenza, Italy

Location

Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS c/o CORE (II piano)

Reggio Emilia, Italy

Location

Ospedale degli Infermi di Rimini

Rimini, Italy

Location

IRCCS-Centro di riferimento oncologico - UO di ematologia e Trapianto Cellule Staminali

Rionero in Vulture, Italy

Location

Policlinico Umberto I - Università "La Sapienza" - Istituto Ematologia -Dipartimento di Biotecnologie Cellulari ed Ematologia

Roma, Italy

Location

Policlinico Universitario Campus Bio-Medico - "Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare"

Roma, Italy

Location

Università Cattolica S. Cuore - Ematologia

Roma, Italy

Location

Istituto Clinico Humanitas - U.O. Ematologia

Rozzano (MI), Italy

Location

Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D'Aragona - U.O. Ematologia

Salerno, Italy

Location

Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

Sassuolo, Italy

Location

Univ. Perugia Sede Terni - Oncoematologia

Terni, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia

Torino, Italy

Location

A.O. C. Panico - U.O.C Ematologia e Trapianto

Tricase, Italy

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Doxorubicin; Bleomycin; Vinblastine; Dacarbazine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Antonio Pinto, MD

  Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - Napoli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study aims to compare the efficacy of two alternative ABVD-based strategies, the first one (Comparator arm) based on a PET-2-adaptation, the second (Experimental arm) relying on a straight dose- and time-intensified schedule, devoid of any PET-adaptation.

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 19, 2017
• Study Start: August 1, 2017
• Primary Completion: November 2, 2021
• Study Completion: November 3, 2024
• Last Updated: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (46)