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

Mantle Cell Lymphoma Clinical Trial

— R2-B  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01737177
• Other study ID #: FIL R2-B
• Status: Completed
• Phase: Phase 2
• First received: November 27, 2012
• Last updated: March 8, 2018
• Start date: July 31, 2012
• Est. completion date: February 2, 2017

Study information

• Verified date: March 2018
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: February 2, 2017
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Italy	SC Ematologia AO SS. Antonio e Biagio e C. Arrigo	Alessandria
Italy	Clinica di Ematologia AOU Umberto I Ospedali Riuniti	Ancona
Italy	Centro di riferimento Oncologico CRO Aviano	Aviano	Pordenone
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	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST Meldola	Meldola	Forlì Cesena
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	Milano
Italy	SC Ematologia AO Niguarda Cà Granda	Milano
Italy	SCDU Ematologia - Università del Piemonte Orientale	Novara
Italy	Medicina Interna 2 ad indirizzo Ematologico AOU San Luigi Gonzaga	Orbassano	Torino
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	IRCCS-Centro di Riferimento Oncologico UO di Ematologia e Trapianto Cellule Staminali	Rionero in Vulture	Potenza
Italy	Ematologia Ospedale S.Camillo Forlanini	Roma
Italy	Ematologia Ospedale San Eugenio	Roma
Italy	Ematologia Università La Sapienza	Roma
Italy	UOC Ematologia AO San Giovanni Addolorata	Roma
Italy	UOC Ematologia e Trapianto Istituto Regina Elena (IFO)	Roma
Italy	Ematologia Istituto Clinico Humanitas	Rozzano	Milano
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	UOC Ematologia Trani	Trani	Barletta-Andria-Trani (BT)
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

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) rate	Proportion of CR according to the Cheson2007 response criteria	At the end of the consolidation phase (6 months)
Primary	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	Toxicity	Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during induction and maintenance therapy	24 months
Secondary	Overall Response Rate (ORR)	ORR at the end of the consolidation treatment is defined as Complete Response(CR) or Partial Response according to the Cheson 2007 response criteria	at the end of the consolidation phase (6 months)
Secondary	Progression Free Survival (PFS) in all patients	PFS will be measured from the day of enrolment and of disease progression or death from any cause	42 months
Secondary	Overall Survival (OS)	OS will be defined as the date of enrolment and the date of recurrence/disease progression or death from any cause	36 months
Secondary	Molecular response rate	rate of conversion to molecular remission measured by PCR	24 months
Secondary	Molecular relapse rate during study period	rate of conversion to molecular relapse measured by PCR	42 months
Secondary	Disease kinetics of minimal residual disease (MRD) during study period	measured by real time PCR in the bone marrow and peripheral blood	up to 42 months
Secondary	Cumulative incidence of second primary malignancies	incidence of any second primary malignancies (haematological and not haematological) diagnosed after the conclusion of induction phase	up to 42 months
Secondary	To evaluate the possible relationship between Cereblon expression and response to therapy	Possible relationship between Cereblon expression and response to therapy	6 months