Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy

Exclusion Criteria

• •Medically apparent central nervous system lymphoma or leptomeningeal disease.
• •History of any other active malignancies.
• •History of any prior cancer curatively treated within the last two years except:
• •* Any non-melanoma skin cancer
• •* Any cancer excised, not treated with chemotherapy and with less than a 30% chance of recurrence within the next 2 years from registration
• •History of any organ transplantation.
• •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• •More than one prior line of any systemic chemoimmunotherapy for follicular lymphoma.
• •Chemotherapy ≤ 21 days prior to first administration of study treatment and/or monoclonal antibody ≥ 3 weeks prior to first administration of study treatment.
• •Prior exposure to radio- or toxin-immunoconjugates.
• •Concurrent use of warfarin or other vitamin K antagonists.
• •Concurrent use of a strong cytochrome P450 (CYP)3A4/5 inhibitor.
• •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug.
• •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• •Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) \>/= 470 msec.
• •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (new York Heart Association \>Class 2), unstable angina, uncontrolled hypertension, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
• •Any uncontrolled active systemic infection or recent infection requiring intravenous anti-infective treatment that was complete ≤ 14 days before the first dose of study drug.
• •Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia.
• •Known history of infection with human immunodeficiency virus (HIV) or history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), or any uncontrolled active systemic infection. Hepatitis B surface antigen must be confirmed negative within on year before enrollment. Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• •Any of the following abnormalities
• •* Absolute neutrophil count (ANC) \<750 cells/mm\^3 (0.75 x 10\^9/L)
• •* Platelet count \<50,000 cells/mm\^3 (50 x 10\^9/L) independent of transfusion support
• •* Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≥3.0 x upper limit of normal (ULN)
• •* Creatinine clearance (CrCl) \<30mL/min
• •* Hemoglobin \<8.0 g/dL
• •* Bilirubin \>1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• •* PT/INR \>1.5 x ULN and PTT (aPTT) \>1.5 x ULN(unless abnormalities are unrelated to coagulopathy or bleeding disorder).
• •Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction.
• •Major surgery planned within 4 weeks of the first dose of study drug.
• •Any life-threatening illness, medical condition, including uncontrolled diabetes mellitus (DM), or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
• •Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib.
• •Lactating or pregnant.
• •Unwilling or unable to participate in all required study evaluations and procedures.
• •Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
• •Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification.