AzTrials
AzTrials

Lymphoma, Mantle-CellPhase 2NCT03567876

Rituximab, Bendamustine and Cytarabine Followed by Venetoclax in High Risk Elderly Patients With MCL

A Phase 2 study testing Venetoclax in people with Lymphoma, Mantle-Cell, run by Fondazione Italiana Linfomi - ETS at 35 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

Prospective, multicenter, phase II trial designed to evaluate whether the addition of Venetoclax after rituximab, bendamustine and cytarabine (R-BAC) to high risk patients with mantle cell lymphoma improves the results of the standard R-BAC, in terms of Progression Free Survival. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Mantle-Cell
What is being tested?
Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
35 sitesItaly
Study dates
3 Sep 2018to 15 Oct 2025
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Previously untreated patients with MCL aged ≥65 years if they are FIT according to the geriatric CGA assessment.
  • age ≤64 years not eliglible to high-dose chemotherapy plus transplantation at physician's judgement (details for non eligibility to be recorded by means of the CIRS, Cumulative Illness rating Scale).
  • Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions.
  • ECOG performance status ≤2.
  • Positivity for cyclin D1 and/or SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative].
  • Adequate renal function (Creatinine clearance >50 mL/min), with preserved diuresis.
Show all 9Show fewer
  • Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) value, total bilirubin <1.5 x ULN, unless directly attributable to the patient's tumor or to congenital causes.
  • Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
  • Written informed consent.

Who cannot join

  • Human immunodeficiency virus (HIV) positive.
  • Previous treatment for lymphoma.
  • Disease confined to the bone marrow/peripheral blood/spleen, without any other nodal or extranodal involvement.
  • In-situ MCL.
  • Medical conditions or organ injuries that could interfere with administration of therapy.
  • Active bacterial, viral, or fungal infection requiring systemic therapy.
Show all 18Show fewer
  • Seizure disorders requiring anticonvulsant therapy.
  • Severe chronic obstructive pulmonary disease with hypoxiemia.
  • History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
  • Uncontrolled diabetes mellitus.
  • Active secondary malignancy.
  • Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.
  • Major surgery within 4 weeks of study Day 1.
  • HBsAg+
  • HCVAb+ patients with active viral replication (HCV-RNA+ with AST>2 x normal limit)
  • Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.
  • CNS involvement
  • Chronic treatment with strong or moderate CYP3A inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole)

Trial locations and contacts

35 sites in 1 country.

35 sites in 1 country

Italy35 sites

  • A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia

    Alessandria

  • Università Politecnica delle Marche, Clinica di Ematologia

    Ancona

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

    Aviano

  • IRCCS Istituto Tumori Giovanni Paolo II, UOC Ematologia

    Bari

  • Policlinico S. Orsola-Malpighi, Istituto di Ematologia "Seragnoli"

    Bologna

  • ASST Spedali Civili, Ematologia

    Brescia

  • Ospedale Businco, Ematologia

    Cagliari

  • Azienda Ospedaliera S. Croce e Carle, SC Ematologia

    Cuneo

  • Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia

    Florence

  • Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Clinica Ematologica

    Genova

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

    Meldola

  • ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

    Milan

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia

    Milan

  • Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia

    Milan

  • Ospedale Maggiore Policlinico - Fondazione IRCCS Ca' Granda, Ematologia

    Milan

  • AOU Maggiore della Carità di Novara, SCDU Ematologia

    Novara

  • Azienda Ospedaliera Universitaria di Padova, Ematologia

    Padova

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

    Palermo

  • IRCCS Policlinico S. Matteo, Divisione di Ematologia

    Pavia

  • Ospedale Guglielmo Da Saliceto, UO Ematologia

    Piacenza

  • Ospedale delle Croci, Ematologia

    Ravenna

  • Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Ematologia

    Reggio Calabria

  • Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia

    Reggio Emilia

  • Ospedale degli Infermi, UO Ematologia

    Rimini

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

    Roma

  • Università Cattolica S. Cuore, Ematologia

    Roma

  • Istituto Clinico Humanitas, UO Ematologia

    Rozzano

  • A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia Universitaria

    Torino

  • A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia

    Torino

  • Ospedale Ca' Foncello, SC Ematologia

    Treviso

  • Azienda Ospedaliera C. Panico, UOC Ematologia e Trapianto

    Tricase

  • Azienda Sanitaria Universitaria Integrata di Udine, Clinica Ematologica

    Udine

  • Ospedale di Circolo, UOC Ematologia

    Varese

  • Azienda Ospedaliera Universitaria Integrata di Verona, UO Ematologia

    Verona

  • Ospedale San Bortolo, Divisione di Ematologia

    Vicenza

Other trials in Italy

About this study

Official title: Rituximab, Bendamustine and Cytarabine Followed by Venetoclax (V-RBAC) in High-risk Elderly Patients With Mantle Cell Lymphoma (MCL)

Prospective, multicenter, phase II trial designed to evaluate whether the addition of Venetoclax after rituximab, bendamustine and cytarabine (R-BAC) to high risk patients with mantle cell lymphoma improves the results of the standard R-BAC, in terms of Progression Free Survival.

Read the detailed description

The aim of the study is to improve long term results of R-BAC, consolidating patients with high-risk (HR) features (defined as: elevated Ki67 and/or blastoid cytology and/or TP53 mutation after central pathology review) with Venetoclax (ABT-199), which has demonstrated relevant single agent activity in relapsed/refractory MCL in a Phase 1-2 trial.

The updated Progression Free Survival curves of the R-BAC500 trial has shown that the expected 2-years PFS for patients with HR disease is 40% (H0), as compared to low-risk patients (LR) that have a 2-years PFS of 100%. The addition of Venetoclax to HR patients after R-BAC is expected to improve results and efficacy of this regimen in this "difficult -to- treat" population, that represents approximately 40-45 % of newly diagnosed elderly patients with MCL. It appears reasonable to treat with the experimental drug also LR patients that do not respond appropriately (less than CR) at the end of R-BAC. Since the number of such LR patients is hardly predictable based on the present experience with R-BAC500 trial, the analysis of this sub-cohort will be of exploratory nature, and thus assessed separately.

The study objective is to evaluate whether the addition of venetoclax after R-BAC to HR patients improves the results of the standard R-BAC, in terms of Progression Free Survival .

Being tested
Venetoclax
Keywords
Mantle cell lymphoma, Elderly patients, First line
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

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

  • VenetoclaxDrug

    Also called Venclyxto (commercial name)

    Consolidation and maintenance phases with Venetoclax (for a total of 2 years) after an induction phase R-BAC (up to 6 cycles for law risk patients and up to 4 cycles for high risk patients)

Study groups in NCT03567876
Study groupRoleWhat they receive
V-RBAC (RBAC followed by Venetoclax)ExperimentalInduction phase: RBAC --> up to 6 cycles for low risk (LR) patients and up to 4 cycles for high risk (HR) patients. Patients proceeding to Venetoclax treatment will receive consolidation with single agent Venetoclax 800 mg/die x 4 28d cycles (with initial ramp-up dose) of each consolidation cycle. Consolidation will be followed by maintenance with single agent Venetoclax 400 mg/die (V maint ) for a total of 2 years (4 months consolidation+20 months maintenance).
Receives: Drug: Venetoclax

What is being measured

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

  1. Progression-free survival of the High Risk patients

    2-years progression-free survival (PFS) of the HR patients from date of enrollment

    Measured: 24 months

Secondary outcomes (7)

  1. Molecular response

    The proportion of molecular response (analyzed in the labs of the FIL- MRD Network)

    Measured: 10 months and 30 months

  2. Progression-free survival of all patients and different subgroups

    The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)

    Measured: 24 months

  3. Overall survival

    Overall survival

    Measured: 54 months

  4. Duration of responses

    Duration of responses

    Measured: 24 months

  5. Proportion of complete remission in High Risk and Law Risk patients

    The proportion of complete remission (CR) before and after venetoclax in the HR group and/or in the LR not responding to R-BAC

    Measured: 6 months and 10 months

  6. Completed expected treatment schedule

    The proportion of patients that complete the expected treatment schedule

    Measured: 30 months

  7. Incidence of Treatment-Emergent Adverse Events

    The proportion of patients with adverse events as assessed by CTCAE 4.03 during venetoclax administration as consolidation or maintenance after R-BAC

    Measured: 10 months and 30 months

Timeline

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

  1. First posted26 Jun 2018
  2. Study start3 Sep 2018
  3. Primary completion26 Jul 2021
  4. Study completion15 Oct 2025

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03567876
Sponsor's protocol ID
FIL_V-RBAC
Status last verified
Dec 2025
First submitted
22 May 2018
Last updated
8 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Moia R, Almasri M, Carazzolo ME, Cividini L, Tabanelli V, Melle F, Genuardi E, Cosentino C, Maher N, Bellia M, Mahmoud AM, Evangelista A, Quaglia FM, Fiori S, Bomben R, Tisi MC, Riva M, Merli A, Di Rotondo F, Corradini P, Farina L, Castellino C, Castellino A, Zilioli VR, Muzi C, Piazza F, Re A, Hohaus S, Rossi Dardanoni FG, Musuraca G, Di Rocco A, Puccini B, Sciarra R, Ballerini F, Cavallo F, Bruna R, Moioli A, Bernardelli A, Patti C, Olivieri J, Bianchi B, Loseto G, Spina M, Usai SV, Stefani PM, Stelitano C, Drandi D, Zinzani PL, Ferreri AJM, Balzarotti M MD, Ladetto M, Ferrero S, Pileri SA, Gaidano G, Visco C. Molecular biomarkers as key determinants of outcome in mantle cell lymphoma: results from the FIL V-RBAC trial. Blood Adv. 2026 Jul 24:bloodadvances.2026020780. doi: 10.1182/bloodadvances.2026020780. Online ahead of print.

    PubMed 42498280

  • Visco C, Tabanelli V, Sacchi MV, Evangelista A, Quaglia FM, Fiori S, Bomben R, Tisi MC, Riva M, Merli A, Rotondo F, Fraenza C, Carazzolo ME, Corradini P, Farina L, Castellino C, Castellino A, Zilioli VR, Muzi C, Piazza F, Re A, Hohaus S, Rossi FG, Musuraca G, Di Rocco A, Puccini B, Sciarra R, Ballerini F, Cavallo F, Bruna R, Moia R, Moioli A, Bernardelli A, Drandi D, Arcari A, Merli F, Gini G, Freilone R, Tani M, Pavone V, Ladetto M, Pileri SA, Balzarotti M; Fondazione Italiana Linfomi. Rituximab, bendamustine, and cytarabine followed by venetoclax in older patients with high-risk mantle cell lymphoma (FIL_V-RBAC): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2025 Oct;12(10):e777-e788. doi: 10.1016/S2352-3026(25)00252-2. Epub 2025 Sep 17.

    PubMed 40975105

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax in people with Lymphoma, Mantle-Cell, run by Fondazione Italiana Linfomi - ETS at 35 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 9 inclusion and 18 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 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 of the High Risk patients (time frame: 24 months). 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 NCT03567876, which also lists 2 linked publications.

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 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in