Bruton's tyrosine kinase (Btk) is non-receptor tyrosine kinase with restricted cellular expression largely limited to B-lymphocytes, monocytes, and mast cells or basophils. Btk is a critical component of the B cell receptor (BCR) signaling network and is crucial for B cell development. Investigation has revealed that some B cell lymphomas and CLL depend on BCR signaling, suggesting that interruption of such signaling could be a promising therapeutic opportunity in B-NHL, CLL and WM.
- Women and men ≥18 years of age
- Body weight ≥50 kg.
- Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop)
- Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment.
- Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months.
- Ability to swallow oral capsules without difficulty
- Has recovered from adverse toxic effects of prior therapies
- Meet the following clinical laboratory requirements:
- Creatinine ≤ 1.5 × upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN
- AST and ALT ≤ 3 × ULN
- Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's)
- Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia)
- Absolute Neutrophil count ≥ 1000/µL
- Prior allogeneic bone marrow transplant
- Autologous stem cell transplant within 3 months of screening
- Active central nervous system involvement
- Subjects with autoimmune hemolytic anemia or immune thrombocytopenia
- Prior treatment with a Btk inhibitor
- Active uncontrolled infection
- History of malabsorption
- Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc.
- History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months
- History of another currently active cancer
- History of major surgery within 4 weeks or minor surgery within 1 week
- Other medical or psychiatric illness or organ dysfunction
- HIV positive
- Positive for Hepatitis B surface antigen or Hepatitis C-virus
Last updated: 09/07/2012
NCT ID: NCT01351935