Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

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.

Inclusion criteria

• 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

Exclusion criteria

• 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