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

NCT03567876 | Completed Phase 2 DMC

• 1 other identifier: FIL_V-RBAC
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 35

Brief 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.

Conditions

Lymphoma, Mantle-Cell

Keywords

Mantle cell lymphoma; Elderly patients; First line

Outcome Measures

Primary Outcomes (1)

• Progression-free survival of the High Risk patients

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

  24 months

Secondary Outcomes (7)

• Molecular response

  10 months and 30 months

• Progression-free survival of all patients and different subgroups

  24 months

• Overall survival

  54 months

• Duration of responses

  24 months

• Proportion of complete remission in High Risk and Law Risk patients

  6 months and 10 months

Study Arms (1)

V-RBAC (RBAC followed by Venetoclax)

EXPERIMENTAL

Induction 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).

Drug: Venetoclax

Interventions

Venetoclax DRUG

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)

Also known as: Venclyxto (commercial name)

V-RBAC (RBAC followed by Venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead
• AbbVie: collaborator

Study Sites (35)

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

Alessandria, Italy

Location

Università Politecnica delle Marche, Clinica di Ematologia

Ancona, Italy

Location

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

Aviano, Italy

Location

IRCCS Istituto Tumori Giovanni Paolo II, UOC Ematologia

Bari, Italy

Location

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

Bologna, Italy

Location

ASST Spedali Civili, Ematologia

Brescia, Italy

Location

Ospedale Businco, Ematologia

Cagliari, Italy

Location

Azienda Ospedaliera S. Croce e Carle, SC Ematologia

Cuneo, Italy

Location

Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia

Florence, Italy

Location

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

Genova, Italy

Location

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

Meldola, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

Milan, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia

Milan, Italy

Location

Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia

Milan, Italy

Location

Ospedale Maggiore Policlinico - Fondazione IRCCS Ca' Granda, Ematologia

Milan, Italy

Location

AOU Maggiore della Carità di Novara, SCDU Ematologia

Novara, Italy

Location

Azienda Ospedaliera Universitaria di Padova, Ematologia

Padua, Italy

Location

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

Palermo, Italy

Location

IRCCS Policlinico S. Matteo, Divisione di Ematologia

Pavia, Italy

Location

Ospedale Guglielmo Da Saliceto, UO Ematologia

Piacenza, Italy

Location

Ospedale delle Croci, Ematologia

Ravenna, Italy

Location

Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Ematologia

Reggio Calabria, Italy

Location

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

Reggio Emilia, Italy

Location

Ospedale degli Infermi, UO Ematologia

Rimini, Italy

Location

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

Roma, Italy

Location

Università Cattolica S. Cuore, Ematologia

Roma, Italy

Location

Istituto Clinico Humanitas, UO Ematologia

Rozzano, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

Ospedale Ca' Foncello, SC Ematologia

Treviso, Italy

Location

Azienda Ospedaliera C. Panico, UOC Ematologia e Trapianto

Tricase, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine, Clinica Ematologica

Udine, Italy

Location

Ospedale di Circolo, UOC Ematologia

Varese, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona, UO Ematologia

Verona, Italy

Location

Ospedale San Bortolo, Divisione di Ematologia

Vicenza, Italy

Location

Related Publications (1)

• 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.

  PMID: 40975105 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Carlo Visco, MD

  AOU Integrata di Verona - U.O. Ematologia -Verona -Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 26, 2018
• Study Start: September 3, 2018
• Primary Completion: July 26, 2021
• Study Completion: October 15, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

IT (35)