Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma

Exclusion Criteria

• •1. Chemotherapy, monoclonal antibody, or small molecule kinase inhibitor less than or equal 21 days prior to first administration of study treatment
• •2. Prior exposure to a Bruton's tyrosine kinase (BTK) or B-cell lymphoma 2 (BCL-2) inhibitor.
• •3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or venetoclax.
• •4. Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome.
• •5. History of other malignancies, except:
• •* Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• •* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• •* Adequately treated carcinoma in situ without evidence of disease.
• •6. Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration \[\>14 days\] of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug.
• •7. Undergone an allogeneic stem cell transplant within the past 1 year.
• •8. Current or history of graft versus host disease
• •9. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• •10. Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
• •12. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
• •13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• •14. Known HIV infection
• •15. Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• •• Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, must have a negative polymerase chain reaction (PCR) result for the respective disease before enrollment. Those who are PCR positive will be excluded.
• •16. Any uncontrolled active systemic infection.
• •17. Major surgery within 4 weeks of first dose of study drug.
• •18. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
• •19. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
• •20. Unable to swallow capsules or tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• •21. Concomitant use of warfarin or other Vitamin K antagonists.
• •22. Requires treatment with a strong cytochrome P450 CYP3A4/5 inhibitor. (Appendix V)
• •23. Richter's transformation confirmed by biopsy.
• •24. Malabsorption syndrome or other condition precluding enteral route of administration.
• •25. Known Central nervous system (CNS) involvement by lymphoma
• •26. Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
• •27. Lactating or pregnant.
• •28. Unwilling or unable to participate in all required study evaluations and procedures.
• •29. 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).
• •30. Currently active, clinically significant hepatic impairment (greater than or equal moderate hepatic impairment according to the Child Pugh classification (see Appendix IX)