This is a prospective, multicenter phase II trial designed to evaluate the safety and activity of the combination of Bendamustine, Lenalidomide and Rituximab (R2-B) in patients with first relapsed/refractory mantle cell lymphoma (MCL) and the efficacy and safety of a maintenance treatment with Lenalidomide for 18 months from the end of R2-B (from month 7 to 24) for those responding to the induction.
This is a phase II study, non randomized, multicenter. Patients with MCL refractory to front line therapy or in first relapse will be enrolled. The study includes an induction phase, a consolidation phase, a maintenance phase and a follow up phase.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
INDUCTION PHASE (COURSE 1-4) * Bendamustine: 70 mg/m2 on day 2 and 3 every 28 * Lenalidomide: 10 mg/daily on day 1 to 14 of a 28 days course * Rituximab: 375 mg/m2 on day 1 every 28 days; only for the first cycle in the induction phase will start on day 8 CONSOLIDATION PHASE (courses 5-6) Patients in CR and PR at the end of the induction phase * Lenalidomide: 15 mg/daily on day 1 to 21 of a 28 days course. * Rituximab: 375 mg/m2 on day 1 every 28 days MAINTENANCE PHASE (courses 7-24) Patients in CR or PR at the end of the consolidation treatment with Lenalidomide until disease progression or unacceptable toxicity up to 18 months (from month 7 to month 24) \- Lenalidomide: 15 mg/daily on day 1 to 21 of a 28 days
Complete Response (CR) rate
Proportion of CR according to the Cheson2007 response criteria
Time frame: At the end of the consolidation phase (6 months)
Maintenance Progression Free Survival (maPFS)
maPFS will be defined in the maintenance cohort as the time between the date of CR/PR and the date of disease progression or death from any cause.
Time frame: 36 months
Toxicity
Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during induction and maintenance therapy
Time frame: 24 months
Overall Response Rate (ORR)
ORR at the end of the consolidation treatment is defined as Complete Response(CR) or Partial Response according to the Cheson 2007 response criteria
Time frame: at the end of the consolidation phase (6 months)
Progression Free Survival (PFS) in all patients
PFS will be measured from the day of enrolment and of disease progression or death from any cause
Time frame: 42 months
Overall Survival (OS)
OS will be defined as the date of enrolment and the date of recurrence/disease progression or death from any cause
Time frame: 36 months
Molecular response rate
rate of conversion to molecular remission measured by PCR
Time frame: 24 months
Molecular relapse rate during study period
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UOC Ematologia Trani
Trani, Barletta-Andria-Trani (BT), Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola
Meldola, Forlì Cesena, Italy
Ematologia Istituto Clinico Humanitas
Rozzano, Milano, Italy
Centro di riferimento Oncologico CRO Aviano
Aviano, Pordenone, Italy
IRCCS-Centro di Riferimento Oncologico UO di Ematologia e Trapianto Cellule Staminali
Rionero in Vulture, Potenza, Italy
Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga
Orbassano, Torino, Italy
SC Ematologia AO SS. Antonio e Biagio e C. Arrigo
Alessandria, Italy
Clinica di Ematologia AOU Umberto I Ospedali Riuniti
Ancona, Italy
SC Ematologia Spedali Civili
Brescia, Italy
Ematologia Ospedale Cardarelli ASREM
Campobasso, Italy
...and 33 more locations
rate of conversion to molecular relapse measured by PCR
Time frame: 42 months
Disease kinetics of minimal residual disease (MRD) during study period
measured by real time PCR in the bone marrow and peripheral blood
Time frame: up to 42 months
Cumulative incidence of second primary malignancies
incidence of any second primary malignancies (haematological and not haematological) diagnosed after the conclusion of induction phase
Time frame: up to 42 months
To evaluate the possible relationship between Cereblon expression and response to therapy
Possible relationship between Cereblon expression and response to therapy
Time frame: 6 months