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

Conditions

Lymphoma, Mantle-Cell

Keywords

Mantle cell lymphoma, Elderly patients, First line

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 .

Riccardo Moia, Mohammad Almasri, Maria Elena Carazzolo, Luca Cividini, Valentina Tabanelli et al. (55 authors)

Blood Advances2026-07-24

10.1182/bloodadvances.2026020780

<i>TP53</i> Mutations in Mantle Cell Lymphoma: From Backup to Game Changer.

Carazzolo ME, Moioli A, Visco C.

2025-11-29

10.3390/jcm14238480

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.

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.

2025-09-17

10.1016/s2352-3026(25)00252-2

Minimal Residual Disease Evaluation in the Context of V-Rbac, a Risk-Tailored Phase II Trial of the Fondazione Italiana Linfomi (FIL)

Riccardo Bomben, Daniela Drandi, Irene Della Starza, Clara Bono, Andrea Evangelista et al. (30 authors)

Blood2024-11-05

10.1182/blood-2024-203004

Rituximab, Bendamustine and Cytarabine Followed By Venetoclax (V-RBAC) in High-Risk Older Patients with Mantle Cell Lymphoma: A Phase 2 Study By the Fondazione Italiana Linfomi (FIL)

Carlo Visco, Valentina Tabanelli, Maria Vittoria Sacchi, Andrea Evangelista, Isacco Ferrarini et al. (40 authors)

Blood2023-11-026 citations

10.1182/blood-2023-179169

Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL

Maria Chiara Tisi, Riccardo Moia, Caterina Patti, Andrea Evangelista, Simone Ferrero et al. (28 authors)

Blood Advances2023-05-1221 citations

10.1182/bloodadvances.2023009744

Interventions

DRUGVenetoclax

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 design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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)

Design outcomes

Primary

Measure	Time frame	Description
Progression-free survival of the High Risk patients	24 months	2-years progression-free survival (PFS) of the HR patients from date of enrollment

Secondary

Measure	Time frame	Description
Progression-free survival of all patients and different subgroups	24 months	The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)
Overall survival	54 months	Overall survival
Duration of responses	24 months	Duration of responses
Molecular response	10 months and 30 months	The proportion of molecular response (analyzed in the labs of the FIL- MRD Network)
Completed expected treatment schedule	30 months	The proportion of patients that complete the expected treatment schedule
Incidence of Treatment-Emergent Adverse Events	10 months and 30 months	The proportion of patients with adverse events as assessed by CTCAE 4.03 during venetoclax administration as consolidation or maintenance after R-BAC
Proportion of complete remission in High Risk and Law Risk patients	6 months and 10 months	The proportion of complete remission (CR) before and after venetoclax in the HR group and/or in the LR not responding to R-BAC

Countries

Italy

Outcome results

None listed