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

NCT ID: NCT03567876

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-03
• Study Completion Date: 2025-10-15

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.

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 .

Conditions

Lymphoma, Mantle-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

V-RBAC (RBAC followed by Venetoclax)

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).

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: 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)

Interventions

Venetoclax

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)

Intervention Type: DRUG

Other Intervention Names

Venclyxto (commercial name)

Eligibility Criteria

Inclusion Criteria

1. Previously untreated patients with MCL aged ≥65 years if they are FIT according to the geriatric CGA assessment.

2. 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).

3. Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions.

4. ECOG performance status ≤2.

5. Positivity for cyclin D1 and/or SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative].

6. Adequate renal function (Creatinine clearance >50 mL/min), with preserved diuresis.

7. 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.

8. 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.

9. Written informed consent.

Exclusion Criteria

1. Human immunodeficiency virus (HIV) positive.

2. Previous treatment for lymphoma.

3. Disease confined to the bone marrow/peripheral blood/spleen, without any other nodal or extranodal involvement.

4. In-situ MCL.

5. Medical conditions or organ injuries that could interfere with administration of therapy.

6. Active bacterial, viral, or fungal infection requiring systemic therapy.

7. Seizure disorders requiring anticonvulsant therapy.

8. Severe chronic obstructive pulmonary disease with hypoxiemia.

9. 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.

10. Uncontrolled diabetes mellitus.

11. Active secondary malignancy.

12. Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.

13. Major surgery within 4 weeks of study Day 1.

14. HBsAg+

15. HCVAb+ patients with active viral replication (HCV-RNA+ with AST>2 x normal limit)

16. 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.

17. CNS involvement

18. Chronic treatment with strong or moderate CYP3A inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlo Visco, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Alessandria, , Italy

Università Politecnica delle Marche, Clinica di Ematologia

Ancona, , Italy

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

Aviano, , Italy

IRCCS Istituto Tumori Giovanni Paolo II, UOC Ematologia

Bari, , Italy

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

Bologna, , Italy

ASST Spedali Civili, Ematologia

Brescia, , Italy

Ospedale Businco, Ematologia

Cagliari, , Italy

Azienda Ospedaliera S. Croce e Carle, SC Ematologia

Cuneo, , Italy

Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia

Florence, , Italy

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

Genova, , Italy

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

Meldola, , Italy

ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia

Milan, , Italy

Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia

Milan, , Italy

Ospedale Maggiore Policlinico - Fondazione IRCCS Ca' Granda, Ematologia

Milan, , Italy

AOU Maggiore della Carità di Novara, SCDU Ematologia

Novara, , Italy

Azienda Ospedaliera Universitaria di Padova, Ematologia

Padua, , Italy

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

Palermo, , Italy

IRCCS Policlinico S. Matteo, Divisione di Ematologia

Pavia, , Italy

Ospedale Guglielmo Da Saliceto, UO Ematologia

Piacenza, , Italy

Ospedale delle Croci, Ematologia

Ravenna, , Italy

Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Ematologia

Reggio Calabria, , Italy

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

Reggio Emilia, , Italy

Ospedale degli Infermi, UO Ematologia

Rimini, , Italy

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

Roma, , Italy

Università Cattolica S. Cuore, Ematologia

Roma, , Italy

Istituto Clinico Humanitas, UO Ematologia

Rozzano, , Italy

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

Torino, , Italy

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

Torino, , Italy

Ospedale Ca' Foncello, SC Ematologia

Treviso, , Italy

Azienda Ospedaliera C. Panico, UOC Ematologia e Trapianto

Tricase, , Italy

Azienda Sanitaria Universitaria Integrata di Udine, Clinica Ematologica

Udine, , Italy

Ospedale di Circolo, UOC Ematologia

Varese, , Italy

Azienda Ospedaliera Universitaria Integrata di Verona, UO Ematologia

Verona, , Italy

Ospedale San Bortolo, Divisione di Ematologia

Vicenza, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 40975105 (View on PubMed)

Other Identifiers

FIL_V-RBAC

Identifier Type: -

Identifier Source: org_study_id