Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Exclusion Criteria

• •Richter transformation of CLL into an aggressive lymphoma
• •History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
• •Prior history of drug-induced colitis or pneumonitis
• •Known hypersensitivity to any of the study drugs
• •Major surgery within 4 weeks prior to screening
• •Central nervous system (CNS) non-Hodgkin lymphoma (NHL); lumbar puncture not required unless CNS involvement is clinically suspected
• •Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects with detectable viral load)
• •Infection with hepatitis B or hepatitis C:
• •* Subjects with a positive hepatitis B surface antigen (HBsAg)) will be excluded
• •* Subjects with or hepatitis C antibody (HCV Ab) will be excluded, unless they have received curative treatment for hepatitis C virus (HCV) and have undetectable viral RNA by PCR.
• •* Subjects with a positive hepatitis B core antibody (HBcAb) must have negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) to be eligible, must receive prophylaxis with entecavir (or equivalent) concomitant with duvelisib treatment, and must be periodically monitored for HBV reactivation by institutional guidelines
• •Investigators who strongly believe that a positive HBcAb is false due to passive immunization from previous immunoglobulin infusion therapy should consider the risk-benefit for the patient given the potential for reactivation
• •Infection with human immunodeficiency virus (HIV): Subjects must be receiving antiretroviral therapy, have undetectable HIV RNA viral load and CD4 cell count greater than or equal to 200/uL to be eligible, must continue antiretroviral therapy concomitant with duvelisib treatment, and must be periodically monitored for suppression of viral load and potential drug-drug interactions between antiretroviral therapy and duvelisib
• •Infection with human T-lymphotropic virus type 1
• •History of tuberculosis treatment within the 2 years prior to randomization
• •History of chronic liver disease, veno-occlusive disease, alcohol abuse, or illicit drug use
• •Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \>20 mg of prednisone (or equivalent) once daily (QD)
• •Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
• •Administration of a live or live attenuated vaccine within 6 weeks of randomization
• •Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention.
• •Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
• •Baseline left ventricular ejection fraction (LVEF) \< 45 percent
• •Baseline QT interval corrected with Fridericia's method (QTcF) \> 500 ms
• •NOTE: criterion does not apply to subjects with a right or left bundle branch block (BBB)
• •Subjects with clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting, or any other condition that will interfere significantly with drug absorption
• •Female subjects who are pregnant or breastfeeding
• •Concurrent active malignancy that requires treatment except malignancies treated with antihormonal therapy alone, nonmelanoma skin cancer, or carcinoma in situ of the cervix.
• •History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening
• •Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes and inflammatory GI diseases such as Crohn s Disease) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the subject associated with his or her participation in the study