Clinical trial NCT01737177: Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL
Official title: Bendamustine, Lenalidomide and Rituximab (R2-B) Combination as a Second-Line Therapy for First Relapsed-Refractory Mantle Cell Lymphomas: A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: MCL
Mantle Cell Lymphoma
RELAPSED-REFRACTORY
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2012-11-29
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Complete Response (CR) rate
timeFrame: At the end of the consolidation phase (6 months)
measure: Maintenance Progression Free Survival (maPFS)
timeFrame: 36 months
Secondary outcomes:
measure: Toxicity
timeFrame: 24 months
measure: Overall Response Rate (ORR)
timeFrame: at the end of the consolidation phase (6 months)
measure: Progression Free Survival (PFS) in all patients
timeFrame: 42 months
measure: Overall Survival (OS)
timeFrame: 36 months
measure: Molecular response rate
timeFrame: 24 months
measure: Molecular relapse rate during study period
timeFrame: 42 months
measure: Disease kinetics of minimal residual disease (MRD) during study period
timeFrame: up to 42 months
measure: Cumulative incidence of second primary malignancies
timeFrame: up to 42 months
measure: To evaluate the possible relationship between Cereblon expression and response to therapy
timeFrame: 6 months
Other outcomes:
Locations:
city: Trani
country: Italy
facility: UOC Ematologia Trani
state: Barletta-Andria-Trani (BT)
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola
state: Forlì Cesena
city: Rozzano
country: Italy
facility: Ematologia Istituto Clinico Humanitas
state: Milano
city: Aviano
country: Italy
facility: Centro di riferimento Oncologico CRO Aviano
state: Pordenone
city: Rionero in Vulture
country: Italy
facility: IRCCS-Centro di Riferimento Oncologico UO di Ematologia e Trapianto Cellule Staminali
state: Potenza
city: Orbassano
country: Italy
facility: Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga
state: Torino
city: Alessandria
country: Italy
facility: SC Ematologia AO SS. Antonio e Biagio e C. Arrigo
city: Ancona
country: Italy
facility: Clinica di Ematologia AOU Umberto I Ospedali Riuniti
city: Brescia
country: Italy
facility: SC Ematologia Spedali Civili
city: Campobasso
country: Italy
facility: Ematologia Ospedale Cardarelli ASREM
city: Caserta
country: Italy
facility: Oncoematologia Ospedale SS. Anna e Sebastiano
city: Catania
country: Italy
facility: UOC Ematologia Osp. Garibaldi Nesima
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese Ciaccio Dipartimento oncoematologico
city: Genova
country: Italy
facility: Clinica Ematologica AOU San Martino
city: Genova
country: Italy
facility: Ematologia AOU S. Martino - IST
city: Latina
country: Italy
facility: UOC Ematologia Universitaria Polo Pontino Sapienza
city: Messina
country: Italy
facility: SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
city: Messina
country: Italy
facility: UOC Ematologia Policlinico Universitario AOU G. Martino
city: Milano
country: Italy
facility: SC Ematologia - Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori
city: Milano
country: Italy
facility: SC Ematologia AO Niguarda Cà Granda
city: Novara
country: Italy
facility: SCDU Ematologia - Università del Piemonte Orientale
city: Palermo
country: Italy
facility: Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello
city: Parma
country: Italy
facility: U.O. Complessa di Ematologia Ospedale di Parma
city: Pavia
country: Italy
facility: Ematologia Policlinico San Matteo
city: Piacenza
country: Italy
facility: Unità Ematologia Ospedale Civile di Piacenza
city: Pisa
country: Italy
facility: UO Ematologia Az Ospedaliera Pisana Ospedale "S.Chiara"
city: Ravenna
country: Italy
facility: UO Ematologia Ospedale Santa Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Divisione di Ematologia AO Bianchi Melacrino Morelli
city: Reggio Emilia
country: Italy
facility: SC Ematologia AO Santa Maria Nuova IRCCS
city: Rimini
country: Italy
facility: UO Oncoematologia ospedale degli Infermi
city: Roma
country: Italy
facility: Ematologia Ospedale San Eugenio
city: Roma
country: Italy
facility: UOC Ematologia e Trapianto Istituto Regina Elena (IFO)
city: Roma
country: Italy
facility: Ematologia Ospedale S.Camillo Forlanini
city: Roma
country: Italy
facility: Ematologia Università La Sapienza
city: Roma
country: Italy
facility: UOC Ematologia AO San Giovanni Addolorata
city: Salerno
country: Italy
facility: Ematologia e Trapianti A.O. San Giovanni di DIO e Ruggi D'Aragona
city: Taranto
country: Italy
facility: Ematologia Ospedale SG Moscati
city: Terni
country: Italy
facility: SC Oncoematologia con autotrapianto AO Santa Maria
city: Torino
country: Italy
facility: SC Ematologia - AO Città della Salute e della Scienza
city: Torino
country: Italy
facility: SC Ematologia U - AO Città della Salute e della Scienza
city: Udine
country: Italy
facility: Clinica Ematologica ASUI Integrata di Udine
city: Varese
country: Italy
facility: Oncologia Medica Varese Ospedale di Circolo e Fondazione Macchi
city: Varese
country: Italy
facility: UO Ematologia Ospedale di Circolo e Fondazione Macchi
Study officials:
affiliation: Clinica Ematologica - Udine - Italy
name: Francesco Zaja, M.D.
role: PRINCIPAL_INVESTIGATOR
References: