Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL
R2-B
Bendamustine, Lenalidomide and Rituximab (R2-B) Combination as a Second-Line Therapy for First Relapsed-Refractory Mantle Cell Lymphomas: A Phase II Study
1 other identifier
interventional
42
1 country
43
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2012
Typical duration for phase_2
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 31, 2012
CompletedFirst Submitted
Initial submission to the registry
November 27, 2012
CompletedFirst Posted
Study publicly available on registry
November 29, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
February 2, 2017
CompletedMarch 9, 2018
March 1, 2018
1.9 years
November 27, 2012
March 8, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Complete Response (CR) rate
Proportion of CR according to the Cheson2007 response criteria
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.
36 months
Secondary Outcomes (9)
Toxicity
24 months
Overall Response Rate (ORR)
at the end of the consolidation phase (6 months)
Progression Free Survival (PFS) in all patients
42 months
Overall Survival (OS)
36 months
Molecular response rate
24 months
- +4 more secondary outcomes
Study Arms (1)
Bendamustina, Lenalidomide, Rituximab
EXPERIMENTAL1 arm for all patients
Interventions
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
Eligibility Criteria
You may qualify if:
- 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;
You may not qualify if:
- 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 - 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (43)
UOC Ematologia Trani
Trani, Barletta-Andria-Trani (BT), 76125, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola
Meldola, Forlì Cesena, 47014, Italy
Ematologia Istituto Clinico Humanitas
Rozzano, Milano, 20089, Italy
Centro di riferimento Oncologico CRO Aviano
Aviano, Pordenone, 33081, Italy
IRCCS-Centro di Riferimento Oncologico UO di Ematologia e Trapianto Cellule Staminali
Rionero in Vulture, Potenza, 85028, Italy
Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga
Orbassano, Torino, 10043, Italy
SC Ematologia AO SS. Antonio e Biagio e C. Arrigo
Alessandria, 15121, Italy
Clinica di Ematologia AOU Umberto I Ospedali Riuniti
Ancona, 60100, Italy
SC Ematologia Spedali Civili
Brescia, 25123, Italy
Ematologia Ospedale Cardarelli ASREM
Campobasso, 86100, Italy
Oncoematologia Ospedale SS. Anna e Sebastiano
Caserta, 81100, Italy
UOC Ematologia Osp. Garibaldi Nesima
Catania, 95100, Italy
Azienda Ospedaliera Pugliese Ciaccio Dipartimento oncoematologico
Catanzaro, 88100, Italy
Clinica Ematologica AOU San Martino
Genova, 16132, Italy
Ematologia AOU S. Martino - IST
Genova, 16132, Italy
UOC Ematologia Universitaria Polo Pontino Sapienza
Latina, 04100, Italy
SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
Messina, 98100, Italy
UOC Ematologia Policlinico Universitario AOU G. Martino
Messina, Italy
SC Ematologia - Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori
Milan, 20133, Italy
SC Ematologia AO Niguarda Cà Granda
Milan, 20162, Italy
SCDU Ematologia - Università del Piemonte Orientale
Novara, 28100, Italy
Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello
Palermo, 90146, Italy
U.O. Complessa di Ematologia Ospedale di Parma
Parma, 43100, Italy
Ematologia Policlinico San Matteo
Pavia, 27100, Italy
Unità Ematologia Ospedale Civile di Piacenza
Piacenza, 29100, Italy
UO Ematologia Az Ospedaliera Pisana Ospedale "S.Chiara"
Pisa, 56100, Italy
UO Ematologia Ospedale Santa Maria delle Croci
Ravenna, 48100, Italy
Divisione di Ematologia AO Bianchi Melacrino Morelli
Reggio Calabria, 89124, Italy
SC Ematologia AO Santa Maria Nuova IRCCS
Reggio Emilia, 42123, Italy
UO Oncoematologia ospedale degli Infermi
Rimini, 47900, Italy
Ematologia Ospedale San Eugenio
Roma, 00144, Italy
UOC Ematologia e Trapianto Istituto Regina Elena (IFO)
Roma, 00144, Italy
Ematologia Ospedale S.Camillo Forlanini
Roma, 00149, Italy
Ematologia Università La Sapienza
Roma, 00161, Italy
UOC Ematologia AO San Giovanni Addolorata
Roma, 00184, Italy
Ematologia e Trapianti A.O. San Giovanni di DIO e Ruggi D'Aragona
Salerno, 84131, Italy
Ematologia Ospedale SG Moscati
Taranto, 74100, Italy
SC Oncoematologia con autotrapianto AO Santa Maria
Terni, 05100, Italy
SC Ematologia - AO Città della Salute e della Scienza
Torino, 10126, Italy
SC Ematologia U - AO Città della Salute e della Scienza
Torino, 10126, Italy
Clinica Ematologica ASUI Integrata di Udine
Udine, 33100, Italy
Oncologia Medica Varese Ospedale di Circolo e Fondazione Macchi
Varese, 21100, Italy
UO Ematologia Ospedale di Circolo e Fondazione Macchi
Varese, 21100, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Francesco Zaja, M.D.
Clinica Ematologica - Udine - Italy
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2012
First Posted
November 29, 2012
Study Start
July 31, 2012
Primary Completion
July 1, 2014
Study Completion
February 2, 2017
Last Updated
March 9, 2018
Record last verified: 2018-03