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.
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 .
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
141
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)
Progression-free survival of the High Risk patients
2-years progression-free survival (PFS) of the HR patients from date of enrollment
Time frame: 24 months
Molecular response
The proportion of molecular response (analyzed in the labs of the FIL- MRD Network)
Time frame: 10 months and 30 months
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)
Time frame: 24 months
Overall survival
Overall survival
Time frame: 54 months
Duration of responses
Duration of responses
Time frame: 24 months
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
Time frame: 6 months and 10 months
Completed expected treatment schedule
The proportion of patients that complete the expected treatment schedule
Time frame: 30 months
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
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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
...and 25 more locations
Time frame: 10 months and 30 months