Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL

NCT ID: NCT01737177

Last Updated: 2018-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2017-02-02

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.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bendamustina, Lenalidomide, Rituximab

1 arm for all patients

Group Type: EXPERIMENTAL

Bendamustine, Lenalidomide, Rituximab

Intervention Type: DRUG

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

Interventions

Bendamustine, Lenalidomide, Rituximab

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Zaja, M.D.

Role: PRINCIPAL_INVESTIGATOR

Clinica Ematologica - Udine - Italy

Locations

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

Oncoematologia Ospedale SS. Anna e Sebastiano

Caserta, , Italy

UOC Ematologia Osp. Garibaldi Nesima

Catania, , Italy

Azienda Ospedaliera Pugliese Ciaccio Dipartimento oncoematologico

Catanzaro, , Italy

Clinica Ematologica AOU San Martino

Genova, , Italy

Ematologia AOU S. Martino - IST

Genova, , Italy

UOC Ematologia Universitaria Polo Pontino Sapienza

Latina, , Italy

SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte

Messina, , Italy

UOC Ematologia Policlinico Universitario AOU G. Martino

Messina, , Italy

SC Ematologia - Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori

Milan, , Italy

SC Ematologia AO Niguarda Cà Granda

Milan, , Italy

SCDU Ematologia - Università del Piemonte Orientale

Novara, , Italy

Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello

Palermo, , Italy

U.O. Complessa di Ematologia Ospedale di Parma

Parma, , Italy

Ematologia Policlinico San Matteo

Pavia, , Italy

Unità Ematologia Ospedale Civile di Piacenza

Piacenza, , Italy

UO Ematologia Az Ospedaliera Pisana Ospedale "S.Chiara"

Pisa, , Italy

UO Ematologia Ospedale Santa Maria delle Croci

Ravenna, , Italy

Divisione di Ematologia AO Bianchi Melacrino Morelli

Reggio Calabria, , Italy

SC Ematologia AO Santa Maria Nuova IRCCS

Reggio Emilia, , Italy

UO Oncoematologia ospedale degli Infermi

Rimini, , Italy

Ematologia Ospedale San Eugenio

Roma, , Italy

UOC Ematologia e Trapianto Istituto Regina Elena (IFO)

Roma, , Italy

Ematologia Ospedale S.Camillo Forlanini

Roma, , Italy

Ematologia Università La Sapienza

Roma, , Italy

UOC Ematologia AO San Giovanni Addolorata

Roma, , Italy

Ematologia e Trapianti A.O. San Giovanni di DIO e Ruggi D'Aragona

Salerno, , Italy

Ematologia Ospedale SG Moscati

Taranto, , Italy

SC Oncoematologia con autotrapianto AO Santa Maria

Terni, , Italy

SC Ematologia - AO Città della Salute e della Scienza

Torino, , 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

UO Ematologia Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Countries

Italy

Other Identifiers

FIL R2-B

Identifier Type: -

Identifier Source: org_study_id