Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Drug: Bendamustine, Lenalidomide, Rituximab
- Registration Number
- NCT01737177
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- Patient has a diagnosis of MCL according to the WHO classification;
- Patient age is ≥ 18 years;
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2;
- Understands and voluntarily signs an informed consent form;
- Able to adhere to the study visit schedule and other protocol requirements;
- Patients treated with one prior regimen and relapsed, or refractory to front line therapy; front line consolidation with autologous stem cell transplantation is considered to be part of first line therapy;
- Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible;
- Adequate haematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L unless due to bone marrow involvement by MCL;
- Conjugated bilirubin up to 2 x ULN unless due to liver involvement by MCL;
- Alkaline phosphatase and transaminases up to 2 x ULN unless due to liver involvement by MCL;
- Creatinine clearance ≥ 30 ml/min; a dose reduction of Lenalidomide for patients with creatinine clearance ≥ 30 mL/min but < 50 mL/min is planned;
- Written informed consent was obtained from the patient prior to any study-specific screening procedures;
- Patient has the ability to swallow capsules or tablets;
- Life expectancy ≥ 6 months;
- Disease free of prior malignancies (a part MCL) with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast;
- Patients who have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study;
- Patient has a history of CNS involvement with lymphoma;
- Patients with previous history of malignancies (a part MCL) ≤ 3 years before study accrual with the exception of currently treated basal cell and squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix;
- History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances;
- Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol;
- Creatinine clearance < 30 ml/min;
- Patient has a known history of HIV seropositivity;
- Patient has active HBV hepatitis. The following categories of HBV positive patients but with non evidence of active hepatitis may be considered for the study and treated with R2-B (see also Section 8.1.8):
- patient is HBsAg + with HBV DNA < 2000 UI/ml (inactive carriers); HBV DNA > 2000 UI/ml is criteria of exclusion;
- patient is HBsAg - HBsAb +;
- patient is HBsAg - but HBcAb +
- Patients with HCV active hepatitis are excluded from the study. Patient with no evidence of active hepatitis and/or advanced chronic liver disease according to liver biopsy or fibro-scan evaluation may be included into the study
- Patients have received previous treatment with either Bendamustine and/or Lenalidomide.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Bendamustina, Lenalidomide, Rituximab Bendamustine, Lenalidomide, Rituximab 1 arm for all patients
- Primary Outcome Measures
Name Time Method Complete Response (CR) rate At the end of the consolidation phase (6 months) Proportion of CR according to the Cheson2007 response criteria
Maintenance Progression Free Survival (maPFS) 36 months 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.
- Secondary Outcome Measures
Name Time Method Toxicity 24 months Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during induction and maintenance therapy
Overall Response Rate (ORR) at the end of the consolidation phase (6 months) ORR at the end of the consolidation treatment is defined as Complete Response(CR) or Partial Response according to the Cheson 2007 response criteria
Progression Free Survival (PFS) in all patients 42 months PFS will be measured from the day of enrolment and of disease progression or death from any cause
Overall Survival (OS) 36 months OS will be defined as the date of enrolment and the date of recurrence/disease progression or death from any cause
Molecular response rate 24 months rate of conversion to molecular remission measured by PCR
Molecular relapse rate during study period 42 months rate of conversion to molecular relapse measured by PCR
Disease kinetics of minimal residual disease (MRD) during study period up to 42 months measured by real time PCR in the bone marrow and peripheral blood
Cumulative incidence of second primary malignancies up to 42 months incidence of any second primary malignancies (haematological and not haematological) diagnosed after the conclusion of induction phase
To evaluate the possible relationship between Cereblon expression and response to therapy 6 months Possible relationship between Cereblon expression and response to therapy
Trial Locations
- Locations (43)
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
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola
🇮🇹Meldola, Forlì Cesena, Italy
Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
UOC Ematologia Osp. Garibaldi Nesima
🇮🇹Catania, Italy
Azienda Ospedaliera Pugliese Ciaccio Dipartimento oncoematologico
🇮🇹Catanzaro, Italy
Ematologia AOU S. Martino - IST
🇮🇹Genova, Italy
SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
🇮🇹Messina, Italy
SCDU Ematologia - Università del Piemonte Orientale
🇮🇹Novara, Italy
Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello
🇮🇹Palermo, Italy
UO Ematologia Az Ospedaliera Pisana Ospedale "S.Chiara"
🇮🇹Pisa, Italy
Ematologia Ospedale S.Camillo Forlanini
🇮🇹Roma, Italy
UOC Ematologia e Trapianto Istituto Regina Elena (IFO)
🇮🇹Roma, Italy
Oncoematologia Ospedale SS. Anna e Sebastiano
🇮🇹Caserta, Italy
SC Ematologia - Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori
🇮🇹Milano, Italy
SC Ematologia AO Santa Maria Nuova IRCCS
🇮🇹Reggio Emilia, Italy
UOC Ematologia AO San Giovanni Addolorata
🇮🇹Roma, Italy
UOC Ematologia Policlinico Universitario AOU G. Martino
🇮🇹Messina, Italy
Unità Ematologia Ospedale Civile di Piacenza
🇮🇹Piacenza, Italy
Divisione di Ematologia AO Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Italy
Ematologia Ospedale SG Moscati
🇮🇹Taranto, Italy
SC Ematologia AO SS. Antonio e Biagio e C. Arrigo
🇮🇹Alessandria, Italy
Ematologia Ospedale Cardarelli ASREM
🇮🇹Campobasso, Italy
Clinica Ematologica AOU San Martino
🇮🇹Genova, Italy
SC Ematologia AO Niguarda Cà Granda
🇮🇹Milano, Italy
Ematologia Ospedale San Eugenio
🇮🇹Roma, Italy
Ematologia Policlinico San Matteo
🇮🇹Pavia, Italy
UO Ematologia Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
UO Oncoematologia ospedale degli Infermi
🇮🇹Rimini, Italy
UO Ematologia Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Ematologia e Trapianti A.O. San Giovanni di DIO e Ruggi D'Aragona
🇮🇹Salerno, Italy
SC Oncoematologia con autotrapianto AO Santa Maria
🇮🇹Terni, Italy
SC Ematologia U - AO Città della Salute e della Scienza
🇮🇹Torino, Italy
Clinica Ematologica ASUI Integrata di Udine
🇮🇹Udine, Italy
Oncologia Medica Varese Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Ematologia Università La Sapienza
🇮🇹Roma, Italy
SC Ematologia - AO Città della Salute e della Scienza
🇮🇹Torino, Italy
Ematologia Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
UOC Ematologia Universitaria Polo Pontino Sapienza
🇮🇹Latina, Italy
UOC Ematologia Trani
🇮🇹Trani, Barletta-Andria-Trani (BT), Italy
Clinica di Ematologia AOU Umberto I Ospedali Riuniti
🇮🇹Ancona, Italy
SC Ematologia Spedali Civili
🇮🇹Brescia, Italy
U.O. Complessa di Ematologia Ospedale di Parma
🇮🇹Parma, Italy