Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia

This is a multicenter open-label phase II study. Primary objective: To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL as measured by the best overall response rate (ORR) during the treatment period. Secondary objectives: * To evaluate the tolerability and the safety of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL * To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL by measuring the overall (OR) and complete response (CR) rate during the study period, the maximum tumor shrinkage, the duration of response, the progression-free survival (PFS) and the overall survival (OS). * To examine the expression of GLI-1 and other Hedgehog (Hh) signalling components in the tumor specimens before and during treatment with vismodegib and corresponding efficacy in patients. 44 patients will be included in the study equally distributed into 4 cohorts according to their histological subtype: * Cohort 1: 11 patients with Diffuse large B-cell lymphomas (DLBCL) * Cohort 2: 11 patients with "indolent" lymphomas (iNHL): Follicular (FL), mantle cell (MCL) and marginal zone lymphoma (MZL) lymphoplasmacytic lymphoma (LPL)/ Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) * Cohort 3: 11 patients with Primary central nervous system lymphomas (PCNSL) * Cohort 4: 11 patients with Chronic lymphocytic leukemia (CLL). After 28 days screening period (Baseline), each patient will be treated by Vismodegib 150 mg per os during for a maximum of 12 months until disease progression, unacceptable toxicities, patient consent withdrawal, death, reasons deemed by the treating physician or study termination by the Sponsor. Tumour assessment (clinical examination, laboratory tests, abdominal and chest CT scan (for PCNSL only at baseline), +/- PET scan for DLBCL, +/- brain MRI and CSF examination and ophthalmic examination for PCNSL, +/- bone marrow examination (except for PCNSL) will be performed at baseline, and then every 2 months during the first 6 months of treatment, and every 3 months thereafter until disease progression or up to 6 months after study treatment stop. Response to treatment will be assessed also by Pharmacodynamic study in tumor samples by immunohistochimic and qPCR analysis at baseline and after one month of treatment with vismodegib. Pharmacokinetic studies (before and after 1 month of treatment) will also be performed. After study treatment discontinuation, the patients will be followed up every 3 months until disease progression or up to 6 months (after 1 year treatement).