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Hodgkin LymphomaPhase 3NCT03159897

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

A Phase 3 study testing Doxorubicin, Bleomycin and Vinblastine in people with Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 46 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Hodgkin Lymphoma
What is being tested?
Doxorubicin, Bleomycin and Vinblastine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
500 participants
Where
46 sitesItaly
Study dates
1 Aug 2017to 3 Nov 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

46 sites in 1 country.

46 sites in 1 country

Italy46 sites

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

    Alessandria

  • Università Politecnica delle Marche, Clinica di Ematologia

    Ancona

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

    Ascoli Piceno

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

    Avellino

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

    Aviano

  • AOU Policlinico Consorziale - U.O. Ematologia con Trapianto

    Bari

  • IRCCS Istituto Tumori Giovanni Paolo II

    Bari

  • Ospedale "Monsignor Raffaele Dimiccoli" - Ematologia

    Barletta

  • A.O. Spedali Civili di Brescia - Ematologia

    Brescia

  • Ospedale Antonio Perrino - Ematologia

    Brindisi

  • Fondazione del Piemonte per l'Oncologia - IRCCS - Ematologia

    Candiolo

  • AORN S.Anna e S. Sebastiano - Oncoematologia

    Caserta

  • Ospedale di Castelfranco Veneto - Ematologia

    Castelfranco Veneto

  • ASST Cremona - Ematologia e CRTO

    Cremona

  • Ospedali Riuniti del Canavese

    Ivrea

  • Ospedale Vito Fazzi - Ematologia

    Lecce

  • Ospedale Madonna delle Grazie - Ematologia

    Matera

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

    Meldola

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

    Messina

  • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

    Milan

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

    Mirano

  • Azienda Ospedaliero-Universitaria Policlinico di Modena - Ematologia

    Modena

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

    Naples

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

    Padova, Padova, 35128

  • Presidio ospedaliero "A. TORTORA"

    Pagani

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

    Palermo

  • AOU di Parma - UO Ematologia e CTMO

    Parma

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

    Pavia

  • AO di Perugia - Ematologia

    Perugia

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

    Pescara

  • Ospedale Guglielmo da Saliceto - U.O.Ematologia

    Piacenza

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

    Potenza

  • Ospedale delle Croci - Ematologia

    Ravenna, Ravenna

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

    Reggio Emilia

  • Ospedale degli Infermi di Rimini

    Rimini

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

    Rionero in Vulture

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

    Roma

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

    Roma

  • Università Cattolica S. Cuore - Ematologia

    Roma

  • Istituto Clinico Humanitas - U.O. Ematologia

    Rozzano (MI)

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

    Salerno

  • Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

    Sassuolo

  • Univ. Perugia Sede Terni - Oncoematologia

    Terni

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

    Torino

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

    Torino

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

    Tricase

Other trials in Italy

About this study

Official title: A Randomized, Open-label, Multicenter, Phase III, 2-arm Study Comparing 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).

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).

Read the detailed description

The study is devoted to patients affected with advanced stage (IIB-IV) Hodgkin Lymphoma.

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.

In the Comparator arm, the patients will receive two courses of standard ABVD (ABVD-28). Those with a PET-2 negative scan (Deauville Score 1-3) will proceed with additional 4 ABVD courses while those with a PET-2-positive scan (Deauville score 4-5) will be diverted towards a deferred intensification with either escalated BEACOPP or HDT plus ASCR , according to the preference of the Center.

In the Experimental arm, patients are treated with three cycles of a dose-dense/dose-intense ABVD (ABVD DD-DI) [e.g. a modified ABVD including the single escalation of doxorubicin to 35 mg/m2 (70 mg/m2 per cycle) and a three-weekly recycle time for all drugs (e.g. administration of all 4 drugs at days 1 and 11 of each cycle)]. Those with a progressive disease or non-responder patients according to PET/CT imaging at interim evaluation (after cycle 3) as categorized with Lugano 2014 Classification will be diverted to salvage strategies. The other patients will receive one additional course of ABVD DD-DI followed by two courses of dose-dense three-weekly ABVD (ABVD DD) (e.g. administration of all four drugs at days 1 and 11 of each cycle at the conventional doses, including doxorubicin at 25 mg/m2).

In both treatment arms 30 Gy Involved Site Radiotherapy (ISRT) is scheduled for those patients PET-negative (DS=3) with residual tumor rests ≥ 2.5 cm and for PET-positive patients in PR (DS= 4 or 5) regardless of the size of the rests. The single reference dose is 2.0 Gy daily and fractionation is five times per week.

Only in the Comparator arm the patients in CR (final score 1-3 according to 5PS by central review panel decision) will receive adjuvant ISRT at the initial bulky site(s) for a total reference dose of 30 Gy in single daily fractions of 2.0 Gy, five times weekly.

Blinded independent central reviewing for PET imaging will supervise response categorization at interim and final PET/CT evaluation.

Being tested
Doxorubicin, Bleomycin, Vinblastine, Dacarbazine
Keywords
advanced stage (IIB-IV), ABVD DD-DI, PET
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxorubicinDrug

    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.

  • BleomycinDrug

    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.

  • VinblastineDrug

    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.

  • DacarbazineDrug

    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.

Study groups in NCT03159897
Study groupRoleWhat they receive
Comparator armExperimentalPatients 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.
Receives: Drug: Doxorubicin; Drug: Bleomycin; Drug: Vinblastine; Drug: Dacarbazine
Experimental armExperimentalDose-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.
Receives: Drug: Doxorubicin; Drug: Bleomycin; Drug: Vinblastine; Drug: Dacarbazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 years

Secondary outcomes (8)

  1. Complete remission rate (CR rate)

    CR rate is defined as the proportion of patients achieving a CR after 2 months of chemotherapy (interim) and at the end of treatment

    Measured: 2 months and 6 months

  2. PET/CT response rate

    PET/CT response rate

    Measured: after 2 months of chemotherapy

  3. Event Free Survival (EFS)

    EFS will be measured from the time from entry onto a study to any treatment failure including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of new treatment lacking documented progression, or death)

    Measured: 3 years

  4. Disease free survival (DFS)

    DFS will be measured from the time of occurrence of disease-free state or attainment of a CR to disease recurrence or death as a result of lymphoma or acute toxicity of treatment

    Measured: 3 years

  5. Overall survival (OS)

    OS is defined as the time from entry onto the clinical trial until death as a result of any cause

    Measured: 3 years

  6. Toxicity

    Acute severe toxicity, acute and delayed pulmonary toxicity, acute and delayed cardiac toxicity. Late toxicity and second malignancies.

    The severity of the toxicities will be classified according to definitions of Common Terminology Criteria for Adverse Event (CTCAE) version 4.3. It will be determined by the incidence of severe, life- threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events (Infusion-related reactions).

    Measured: 6 months for acute toxicity and 5 years for late toxicity

  7. Quality of life (QoL)

    QoL will be measured at the baseline, the end of therapy and during follow-up through the EORTC QLQ-C30 questionnaire

    Measured: 36 months

  8. Cost-effectiveness analyses

    Cost-effectiveness analyses. ICER will be calculated by dividing the difference in mean total costs arms by the difference in the mean effects. The ICER will be calculated for the principal clinical effect measures of the trial. (i.e. PFS) and for QALYs. QALYs will be calculated multiplying the amount of time a patient spent in a particular health state by the utilities estimated using the EQ-5D questionnaires

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start1 Aug 2017
  3. Primary completion2 Nov 2021
  4. Study completion3 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
500 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03159897
Sponsor's protocol ID
FIL-Rouge
Status last verified
Jul 2025
First submitted
15 May 2017
Last updated
8 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Doxorubicin, Bleomycin and Vinblastine in people with Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 46 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03159897.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2025.

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