Patients with first relapsed/refractory mantle cell lymphoma (MCL) MedDRA version: 14.1 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Trade Name: REVLIMID
Pharmaceutical Form: Tablet
INN or Proposed INN: LENALIDOMIDE
CA
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1-Patient has a diagnosis of MCL according to the WHO classification; 2-Patient age is = 18 years; 3-Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of = 2; 4-Understands and voluntarily signs an informed consent form; 5-Able to adhere to the study visit schedule and other protocol requirements; 6-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; 7-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; 8-Adequate haematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L unless due to bone marrow involvement by MCL; 9-Conjugated bilirubin up to 2 x ULN unless due to liver involvement by MCL; 10-Alkaline phosphatase and transaminases up to 2 x ULN unless due to liver involvement by MCL; 11-Creatinine clearance = 30 ml/min; a dose reduction of Lenalidomide for patients with creatinine clearance = 30 mL/min but =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1-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 nontreatment studies is allowed, if it will not interfere with participation in this study; 2-Patient has a history of CNS involvement with lymphoma; 3-Patients with previous history of malignancies (a part MCL) = 3 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; 4-History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances; 5-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; 6-Creatinine clearance 2000 UI/ml is criteria of exclusion; - patient is HBsAg – HBsAb +; - patient is HBsAg – but HBcAb + 9-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 (see also Section 8.1.9); 10-Patients have received previous treatment with either Bendamustine and/or Lenalidomide.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To explore the antitumor activity of the association of R2-B in terms of complete response (CR) in patients with relapsed/refractory MCL to a first line of therapy. 2.To evaluate the efficacy of a maintenance treatment with Lenalidomide for 18 months from the end of R2-B (from month 7 to 24) for those responding (CR or PR) to the induction, in terms of progression free survival (maPFS).;Secondary Objective: 1.To evaluate the safety profile; 2.To evaluate the molecular response (MR); 3.To evaluate the overall response (OR); 4.To evaluate the effect of treatment on Progression Free Survival (PFS); 5.To evaluate the effect of treatment on Overall Survival (OS); 6.To estimate the cumulative incidence of second primary malignancies (hematological and not-hematological).;Primary end point(s): 1-the complete response (CR) rate after consolidation in all included patients according to Cheason Criteria; 2-the maPFS in the subset of patients with CR or PR, receiving the maintenance regimen. maPFS in the maintenance cohort will be defined as the time between the date of CR/PR and the date of disease progression or death from any cause. Patients without events will be censored at the last follow up visit.;Timepoint(s) of evaluation of this end point: 1-the complete response (CR) rate after consolidation in all included patients; 2-the maPFS in the subset of patients with CR or PR, receiving the maintenance regimen. maPFS in the maintenance cohort will be defined as the time between the date of CR/PR and the date of disease progression or death from any cause. Patients without events will be censored at the last follow up visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Any grade III or higher toxicities will be recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (October 1, 2009). Toxicity events will be determined by the incidence of severe, life- threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events commencing after the first induction dose or at any time during maintenance therapy; 2-Overall response rate (CR+PR) will be assessed at the end of the consolidation treatment; 3-Progression Free Survival (PFS) in all patients will be defined as the time between the date of enrolment and the date of recurrence/disease progression or death from any cause. Patients without events will be censored at the last follow up visit; 4-Overall Survival (OS) will be defined as the time between the date of enrollement (or the date of the end of consolidation for the maintenance cohort) and the date of death from any cause. Patients alive at the end of follow-up will be censored at the last follow up visit; 5-Rate of conversion to molecular remission, rate of molecular relapse, disease kinetics by real time PCR in the BM and PB will be assessed to evaluate the activity of Lenalidomide maintenance on MRD; 6-The cumulative incidence (in the maintenance cohort) of any second primary malignancies (hematological and not-hematological), diagnosed after the conclusion of the induction phase, will be analysed considering deaths as competing events.;Timepoint(s) of evaluation of this end point: 1-Any grade III or higher toxicities (CTCAE 4.0) 2-CR+PR at the end of the consolidation treatment; 3-PFS in all patients between date of enrolment and date of recurrence/disease progression or death from any cause; 4-OS between date of enrollement (or date of the end of consolidation for the maintenance cohort) and the date of death from any cause. 5-Rate of conversion to molecular remission, rate of molecular relapse, disease kin | — |
Countries
Italy
Contacts
Public ContactSegreteria FIL
Segreteria Fondazione Italiana Linfomi Onlus
Outcome results
None listed