A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL

Exclusion Criteria

• •1. Transformed CLL, including Hodgkin and non-Hodgkin lymphoma
• •2. Active autoimmune hemolytic anemia or thrombocytopenia
• •3. Known bleeding disorders
• •4. Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless due to Gilbert's disease, aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of liver, Child-Pugh class B or C
• •5. Impaired renal function: estimated glomerular filtration rate (GFR) \< 30ml/min/1.73m(2) based on CKD-EPI
• •6. Life-threatening illness, medical condition or organ system dysfunction which, in the investigators opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib and fludarabine, or put the study outcomes at undue risk
• •7. Concomitant immunomodulatory therapy, chemotherapy, radiotherapy or experimental therapy
• •8. Active Hepatitis B or Hepatitis C infection
• •9. HIV infection
• •10. Female patients who are currently in pregnancy, or unwilling to use acceptable methods of contraception or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol.
• •11. Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.
• •12. Unable to understand the investigational nature of the study or give informed consent.
• •13. Individuals \< 18 years old
• •14. Known hypersensitivity to any component of ibrutinib or fludarabine
• •15. Requires concomitant anticoagulation with Coumadin (warfarin) or other vitamin K antagonists.
• •16. 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 greater than or equal to 2 years or which will not limit survival to \< 2 years
• •17. 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
• •18. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug
• •19. Major surgery within 4 weeks of first dose of study drug
• •20. Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification, or a history of myocardial infarction or unstable angina, or acute coronary syndrome within 6 months of screening.
• •21. Subjects who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitor.