Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive B-cell Lymphoma

Inclusion Criteria: * Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients * Phase II: Patients with either histologically documented CD20-positive Diffuse large-cell lymphoma or Mantle cell lymphoma (cohort 1) or follicular lymphoma, WHO grade 1, 2 or 3a (cohort 2-3-4) * Phase IB and II: * Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option (cohort 2 only) * Aged 18 years or more * ECOG performance status 0, 1 or 2 * At least one bi-dimensionally measurable nodal or tumor lesion defined by CT scan as: greatest transverse diameter \> 1.5 cm and a short axis ≥ 10mm * Signed inform consent * Life expectancy ≥ 3 months. * All subjects must be able to understand and fulfill the lenalidomide Pregnancy Prevention Plan requirements (see in appendix) * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 2 months after discontinuation of all study treatments. Exclusion Criteria: * Previous treatment with obinutuzumab or lenalidomide * Known CD20 negative status at relapse/progression. Biopsy at relapse/progression is recommended but not mandatory * Central nervous system or meningeal involvement by lymphoma * Contraindication to any drug contained in the study treatment regimen * Known HIV or HTLV-1 infection, positive serology to HB surface antigen \[HBsAg\] or total HB core antibody \[anti-HB-c\]) and Hepatitis C (Hepatitis C virus \[HCV\] antibody) * Any serious active disease or co-morbid medical condition (such as New York Heart Association Class II or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision) * Any of the following laboratory abnormalities unless secondary to underlying lymphoma: * Absolute neutrophil count (ANC) \< 1,500 cells/mm3 (1.5 x 109/L). * Platelet count \< 100,000/mm3 (100 x 109/L) unless due to lymphoma for phase II part. * Serum SGOT/AST or SGPT/ALT 3.0 x upper limit of normal (ULN) unless disease involvement. * Serum total bilirubin \> 2.0 mg/dL (34 μmol/L), except if disease related or in case of Gilbert syndrome * Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of \< 50 mL /min. For phase II part of the study, patients with calculated creatinine clearance between 30 and 50ml/min can be included and lenalidomide dose will be adjusted as follows (10mg once daily) * Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 5 years * Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or lactating females. * Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide. * Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide. * Subjects with ≥ Grade 2 neuropathy. * Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy * Patients taking corticosteroids during 4 weeks before inclusion, unless administered at a dose equivalent to ≤ 10 mg/day prednisone (over these 4 weeks) * Prior history of Progressive Multifocal Leukoencephalopathy (PML)