Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL

Inclusion Criteria

• A diagnosis of CLL/ SLL and have not been previously treated.
• An indication for treatment by 2008 IWCLL Criteria.
• Male and female subjects of age >/= 18 years at the time of signing informed consent and requiring treatment within the next 2 to 6 months.
• Understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations.
• Platelet counts at study entry must be greater than 50,000/µL and absolute neutrophil counts at study entry must be greater than 750/µL.
• Free of prior malignancies for 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast.
• Subjects must be able to contribute the required amount of blood and/or tissue without compromising their well-being or care and must weigh at least 110 pounds.
• Adequate renal and hepatic function as indicated by all of the following: total bilirubin 30 mL/min, as calculated by the Cockcroft-Gault equation.
• Participants must be willing to be contacted again for consideration of additional studies in the future, such as a blood draw or another action (e.g., bone marrow aspiration and/or biopsy) that would be associated with their standard of care, unless they consented to such for research purposes.
• An Eastern Cooperative Oncology (ECOG)/World Health Organization (WHO) performance status of 0-2.
• Males and females of child bearing potential must have adequate birth control protection while on study and for 30 days after the last dose of study drug. The couple will use two forms of birth control for the entire time of the study and 30 days after finishing study. Conception control should include a hormonal method (birth control pill, etc.), and a double-barrier methods (condoms with spermicidal, sponge with spermicidal, or diaphragm with spermicidal), or abstinence (not having sex) will be practiced.
• Female subjects will need a negative pregnancy screening test if they are of child bearing potential.

Exclusion Criteria

• Subjects less than 18 years of age.
• A lymphocyte doubling time of 60 mg daily or equivalent), or immunotherapy prior to enrollment or concurrent with this trial.
• Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells such as: Phosphodiesterase inhibitors (PDE-inhibitors) (e.g., sildenafil, theophylline), immunosuppressive agents (e.g., prednisone, cyclosporin-A, rapamycin), green tea extract, itraconazole, ketoconazole, clarithromycin, bupropion, and Cox-2 inhibitors.
• Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Subjects with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP).
• Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the subject at undue risk to undergo therapy with PCI-32765.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study.
• History of intracranial hemorrhage or stroke within 6 months prior to the study.
• Evidence of bleeding diathesis or coagulopathy.
• Major surgical procedure, open biopsy, or significant traumatic injury, within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study. (Minor surgical procedures, fine needle aspirations or core biopsies with