Efficacy and Safety of Ibrutinib in Patients With CLL and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers

Inclusion Criteria:

1. Adult patients between age of 18 - 80 years
2. Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab
3. Pathologically proven B-cell lymphoproliferative neoplasms including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone B-cell lymphoma, and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma).
4. Pathologically proven follicular lymphoma, with relapse or disease progression \> 12 months after previous rituximab therapy.
5. Chronic HBV carriers (HBsAg+)
6. Occult HBV carriers (HBsAg-, anti-HBc+ and HBV DNA-)
7. Haematology values within the following limits:

   1. Absolute neutrophil count (ANC)1000/mm3 independent of growth factor support
   2. Platelets 100,000/mm3, or 50,000/mm3 if bone marrow is involved, and independent of transfusion support in either situation
8. Biochemical values within the following limits:

   1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN)
   2. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
   3. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft Gault) ≥ 40 mL/min/1.73m2
9. Competent to give an informed consent

Exclusion Criteria:

1. Concomitant chronic liver diseases not related to HBV
2. Known history of drug-induced liver injury, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver and portal hypertension
3. Known history of drug induced pneumonitis
4. Known history of inflammatory bowel disease
5. Woman who are pregnant or breast-feeding
6. Patients who do not consent to the use of effective contraception during the study
7. Active infections.
8. Evidence of ongoing active HBV hepatitis (ALT and/or AST \> 2x upper limit of normal, and detectable HBV DNA)
9. Patients known to have histological transformation of CLL to an aggressive lymphoma
10. Vaccinated with live, attenuated vaccines within 4 weeks of enrolment