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

Inclusion Criteria

• •Histologically confirmed diagnosis of B-cell lymphoma (DLBCL, MCL, FL, MZL, LPL/WM, SLL or PCNSL) or CLL (Matutes score ≥4) requiring treatment that is recurrent after at least one prior therapy for which no potentially curative therapy nor better treatment option is available. Specifically, the patient should have received all treatments considered to be standards of care, including stem cell transplantation (when appropriate, if patient eligible), and agents known to have significant clinical efficacy in their disease.Patient must be eligible for tumor biopsy. Biopsy at relapse is mandatory for all patients except for PCNSL (optional) and should provide enough tumor tissue for biological tests (paraffin-embedded and frozen or RNAlater-conserved tissue).
• •Age 18 and older
• •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• •Signed inform consent
• •Life expectancy ≥ 3 months
• •Patients who have received up to a maximum of 4 lines of treatment (including radiotherapy)
• •Patients must have recovered from all toxicities related to prior treatments to ≤ grade 1.
• •Adequate Laboratory Parameters (unless abnormalities are related to underlying disease) within 28 days prior to signing informed consent, including:
• •* Absolute neutrophil count (ANC) ≥ 1000/μL
• •* Platelet ≥ 75,000/μL
• •* Hemoglobin \> 8.5 g/dL
• •* Total bilirubin ≤ 1.5 x upper limit of normal (UNL)
• •* Hepatic enzymes (AST, ALT) ≤ 3 x institutional ULN
• •Measurable disease:
• •* Cohort 1 and 2 (DLBCL and iNHL): Bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter.
• •* Cohort 3 (PCNSL): Measurable PCNSL on MRI with gadolinium enhancement (no minimal size) or, for intraocular lymphoma (IOL), measurable disease at fundoscopic examination with elevated level of IL10 (\>10 pg/ml) in the acqueous humor.
• •* Cohort 4 (CLL): Measurable disease assessable in the blood (lymphocytosis, cytopenia) and/or by imaging (bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter)
• •Patient must be able to take oral medication
• •Females of childbearing potential (FCBP) must :
• •* have a negative pregnancy test (serum or urine, sensitivity \< or = 25IU HCG/L) within 96 hours prior to starting study drug administration.
• •* Agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual contact during whole treatment period and up to 7 months after discontinuation of study drug treatment
• •Male patients must agree :
• •* to use a condom with female of childbearing potential or to practice complete abstinence during whole treatment period and up to 7 months after discontinuation of study drug treatment.
• •* To abstain from donating semen during whole treatment period and up to 7 months after discontinuation of study drug treatment
• •For all patients receiving vismodegib (GDC-0449):
• •* To agree to abstain from donating blood during the whole study and for at least 7 months after discontinuation of study drug treatment
• •* To agree not to share the study medication with another person