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Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL (R2-B)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01737177
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : March 9, 2018
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

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.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Drug: Bendamustine, Lenalidomide, Rituximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 31, 2012
Actual Primary Completion Date : July 2014
Actual Study Completion Date : February 2, 2017

Arm Intervention/treatment
Experimental: Bendamustina, Lenalidomide, Rituximab
1 arm for all patients
Drug: Bendamustine, Lenalidomide, Rituximab


  • 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


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

Primary Outcome Measures :
  1. Complete Response (CR) rate [ Time Frame: At the end of the consolidation phase (6 months) ]
    Proportion of CR according to the Cheson2007 response criteria

  2. Maintenance Progression Free Survival (maPFS) [ Time Frame: 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 :
  1. Toxicity [ Time Frame: 24 months ]
    Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during induction and maintenance therapy

  2. Overall Response Rate (ORR) [ Time Frame: 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

  3. Progression Free Survival (PFS) in all patients [ Time Frame: 42 months ]
    PFS will be measured from the day of enrolment and of disease progression or death from any cause

  4. Overall Survival (OS) [ Time Frame: 36 months ]
    OS will be defined as the date of enrolment and the date of recurrence/disease progression or death from any cause

  5. Molecular response rate [ Time Frame: 24 months ]
    rate of conversion to molecular remission measured by PCR

  6. Molecular relapse rate during study period [ Time Frame: 42 months ]
    rate of conversion to molecular relapse measured by PCR

  7. Disease kinetics of minimal residual disease (MRD) during study period [ Time Frame: up to 42 months ]
    measured by real time PCR in the bone marrow and peripheral blood

  8. Cumulative incidence of second primary malignancies [ Time Frame: up to 42 months ]
    incidence of any second primary malignancies (haematological and not haematological) diagnosed after the conclusion of induction phase

  9. To evaluate the possible relationship between Cereblon expression and response to therapy [ Time Frame: 6 months ]
    Possible relationship between Cereblon expression and response to therapy

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01737177

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UOC Ematologia Trani
Trani, Barletta-Andria-Trani (BT), Italy, 76125
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola
Meldola, Forlì Cesena, Italy, 47014
Ematologia Istituto Clinico Humanitas
Rozzano, Milano, Italy, 20089
Centro di riferimento Oncologico CRO Aviano
Aviano, Pordenone, Italy, 33081
IRCCS‐Centro di Riferimento Oncologico UO di Ematologia e Trapianto Cellule Staminali
Rionero in Vulture, Potenza, Italy, 85028
Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga
Orbassano, Torino, Italy, 10043
SC Ematologia AO SS. Antonio e Biagio e C. Arrigo
Alessandria, Italy, 15121
Clinica di Ematologia AOU Umberto I Ospedali Riuniti
Ancona, Italy, 60100
SC Ematologia Spedali Civili
Brescia, Italy, 25123
Ematologia Ospedale Cardarelli ASREM
Campobasso, Italy, 86100
Oncoematologia Ospedale SS. Anna e Sebastiano
Caserta, Italy, 81100
UOC Ematologia Osp. Garibaldi Nesima
Catania, Italy, 95100
Azienda Ospedaliera Pugliese Ciaccio Dipartimento oncoematologico
Catanzaro, Italy, 88100
Clinica Ematologica AOU San Martino
Genova, Italy, 16132
Ematologia AOU S. Martino - IST
Genova, Italy, 16132
UOC Ematologia Universitaria Polo Pontino Sapienza
Latina, Italy, 04100
SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
Messina, Italy, 98100
UOC Ematologia Policlinico Universitario AOU G. Martino
Messina, Italy
SC Ematologia ‐ Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori
Milano, Italy, 20133
SC Ematologia AO Niguarda Cà Granda
Milano, Italy, 20162
SCDU Ematologia ‐ Università del Piemonte Orientale
Novara, Italy, 28100
Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello
Palermo, Italy, 90146
U.O. Complessa di Ematologia Ospedale di Parma
Parma, Italy, 43100
Ematologia Policlinico San Matteo
Pavia, Italy, 27100
Unità Ematologia Ospedale Civile di Piacenza
Piacenza, Italy, 29100
UO Ematologia Az Ospedaliera Pisana Ospedale "S.Chiara"
Pisa, Italy, 56100
UO Ematologia Ospedale Santa Maria delle Croci
Ravenna, Italy, 48100
Divisione di Ematologia AO Bianchi Melacrino Morelli
Reggio Calabria, Italy, 89124
SC Ematologia AO Santa Maria Nuova IRCCS
Reggio Emilia, Italy, 42123
UO Oncoematologia ospedale degli Infermi
Rimini, Italy, 47900
Ematologia Ospedale San Eugenio
Roma, Italy, 00144
UOC Ematologia e Trapianto Istituto Regina Elena (IFO)
Roma, Italy, 00144
Ematologia Ospedale S.Camillo Forlanini
Roma, Italy, 00149
Ematologia Università La Sapienza
Roma, Italy, 00161
UOC Ematologia AO San Giovanni Addolorata
Roma, Italy, 00184
Ematologia e Trapianti A.O. San Giovanni di DIO e Ruggi D'Aragona
Salerno, Italy, 84131
Ematologia Ospedale SG Moscati
Taranto, Italy, 74100
SC Oncoematologia con autotrapianto AO Santa Maria
Terni, Italy, 05100
SC Ematologia - AO Città della Salute e della Scienza
Torino, Italy, 10126
SC Ematologia U - AO Città della Salute e della Scienza
Torino, Italy, 10126
Clinica Ematologica ASUI Integrata di Udine
Udine, Italy, 33100
Oncologia Medica Varese Ospedale di Circolo e Fondazione Macchi
Varese, Italy, 21100
UO Ematologia Ospedale di Circolo e Fondazione Macchi
Varese, Italy, 21100
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
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Principal Investigator: Francesco Zaja, M.D. Clinica Ematologica - Udine - Italy

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Responsible Party: Fondazione Italiana Linfomi ONLUS Identifier: NCT01737177     History of Changes
Other Study ID Numbers: FIL R2-B
First Posted: November 29, 2012    Key Record Dates
Last Update Posted: March 9, 2018
Last Verified: March 2018
Keywords provided by Fondazione Italiana Linfomi ONLUS:
Mantle Cell Lymphoma
Additional relevant MeSH terms:
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Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action