The purpose of this study is to establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma.

Inclusion Criteria:

• Women and men ≥ 18 years of age. There is no experience with this drug in a pediatric population.
• Body weight ≥ 40 kg.
• Recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (NHL) according to WHO classification, including small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL) lymphoplasmacytic lymphoma, including Waldenström's Macroglobulinemia (WM), and pre-identified DLBCL ABC subtype oFor the DLBCL-ABC cohort, documented, activated B-cell subtype by either immunohistochemistry or tissue microarray analysis.
• Measurable disease (for NHL, bidimensional disease ≥ 2 cm diameter in at least one dimension, for CLL ≥ 5000 leukemia cells/mm3, for WM presence of immunoglobulin M paraprotein with a minimum IgM level ≥ 1000 mg/dL and infiltration of bone marrow by lymphoplasmacytic cells), and pre-identified DLBCL ABC subtype by immunohistochemistry (IHC).
• Have failed ≥ 1 previous treatment for lymphoma and no standard therapy is available. Patients with diffuse large B cell lymphoma must have failed, refused or be ineligible for autologous stem cell transplant.
• ECOG performance status of ≤ 1.
• Ability to swallow oral capsules without difficulty.
• Willing and able to sign a written informed consent.

Exclusion Criteria:

• More than four prior systemic therapies (not counting maintenance rituximab), except for CLL patients. Salvage therapy/conditioning regimen leading up to autologous bone marrow transplantation is considered to be one regimen (This inclusion criterion does not apply to the DLBCL-ABC cohort).

• Prior allogeneic bone marrow transplant.

• Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing.

• Major surgery within 4 weeks before first day of study drug dosing.

• CNS involvement by lymphoma.

• Active opportunistic infection or treatment for opportunistic infection within 4 weeks before first day of study drug dosing.

• History of malabsorption.

• Laboratory abnormalities:

  • Creatinine > 1.5 × institutional upper limit of normal (ULN)
  • Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
  • AST or ALT > 2.5 × institutional ULN
  • Platelet count < 75,000/µL (unless patients have CLL and bone-marrow involvement, provided they are not transfusion-dependent)
  • Absolute neutrophil count (ANC) < 1500/µL (unless patients have CLL and bone-marrow involvement)
  • Hgb < 8.0 g/dL

• Uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements.

• Risk factors for, or use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes within 7 days of treatment start.

• QTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.

• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.

• Known HIV infection.

• Hepatitis B sAg or Hepatitis C positive.

• Other medical or psychiatric illness or organ dysfunction which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent.

• Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound).

• Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.

• History of prior cancer < 2 years ago, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.