Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL
Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL
The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily
 regimen of orally administered PCI-32765 combined with ofatumumab in subjects with
 relapsed/refractory CLL/SLL and related diseases
Inclusion Criteria:

 1. Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small
 lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or Richter's transformation
 arising out of CLL/SLL as defined by WHO classification of hematopoietic neoplasms and
 satisfying ≥ 1 of the following conditions:

 -  Progressive splenomegaly and/or lymphadenopathy identified by physical
 examination or radiographic studies

 -  Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow
 involvement

 -  Presence of unintentional weight loss > 10% over the preceding 6 months

 -  NCI CTCAE Grade 2 or 3 fatigue

 -  Fevers > 100.5 degree or night sweats for > 2 weeks without evidence of infection

 -  Progressive lymphocytosis with an increase of > 50% over a 2 month period or an
 anticipated doubling time of < 6 months

 -  Need for cytoreduction prior to stem cell transplant

 2. Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or
 ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to
 such therapy

 3. 10% expression of CD20 on CLL/SLL cells

 4. ECOG performance status ≤ 2

 5. Life expectancy ≥ 12 weeks

 6. Subjects must have organ and marrow function as defined below:

 -  Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow
 involvement

 -  Platelets ≥ 30,000/μL in the absence of bone marrow involvement

 -  Total bilirubin ≤ 1.5 x institutional upper limit of normal unless due to
 Gilbert's disease

 -  AST (SGOT) ≤ 2.5 x institutional upper limit of normal unless due to infiltration
 of the liver

 -  Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min

 7. No history of prior exposure to ofatumumab

 8. Age ≥ 18 years

 9. Body weight ≥ 40 kg

 Exclusion Criteria:

 1. A life-threatening illness, medical condition or organ system dysfunction which, in
 the investigator's opinion, could compromise the subject's safety, interfere with the
 absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk

 2. Significant cardiovascular disease

 3. Any condition which could interfere with the absorption or metabolism of PCI-32765
 including unable to swallow capsules, malabsorption syndrome, disease significantly
 affecting gastrointestinal function, or resection of the stomach or small bowel or
 ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete
 bowel obstruction

 4. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis
 C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection

 5. Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy
 within 4 weeks before first dose of study drug. Corticosteroids for disease-related
 symptoms are allowed provided 1 week washout occurs

 6. Active central nervous system (CNS) involvement by lymphoma

 7. Major surgery within 4 weeks before first dose of study drug

 8. Lactating or pregnant

 9. Known moderate to severe chronic obstructive pulmonary disease (COPD)

 10. History of prior malignancy, except for adequately treated basal cell or squamous cell
 skin cancer, in situ cervical cancer, or other cancer from which the subject has been
 disease free for at least 2 years or which will not limit survival to < 2 years

 11. History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including
 radiation