Clinical trial with Ibrutinib and Venetoclax for patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Prior treatment

• Previous treatment with BTK and/or BCL2 inhibitors (patients previously treated with PI3K inhibitors are eligible)
• Requires the use of warfarin, marcumar, or phenprocoumon (potential drug-drug interaction increasing exposure of warfarin or phenprocoumon): low molecular weight drugs e.g. heparin are acceptable
• Treatment, administration or consumption of any of the following within 3 days prior to the first dose of venetoclax (see also Appendix G). a. Strong Cytochrome P450 3A (CYP3A) inhibitors b. Moderate CYP3A inhibitors c. Moderate or strong CYP3A inducers d. PI3K inhibitors (e.g. Idelalisib); e. Grapefruit or grapefruit products f. Seville oranges (including marmalade containing Seville oranges) g. Star fruit

Other illness

• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• History of other malignancies, except: a. 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. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without current evidence of disease.

Other

• Transformation of CLL to aggressive NHL (Richter’s transformation or pro-lymphocytic leukemia)
• Known central nervous system (CNS) involvement
• Inadequate renal function: CrCl <30 mL/min

• Documented CLL requiring treatment according to the IWCLL criteria (Hallek et al. 2008)
• Relapsed/refractory CLL patients who received at least 1 prior therapy
• Adequate bone marrow function without transfusion < 2 weeks of screening as follows: a. Absolute neutrophil count (ANC) =1.0 x 109/L (growth factors administration is allowed) b. Platelets =30 x 109/L. If thrombocytopenia due to BM involvement, platelets should be = 20 x 109/L c. Hemoglobin value =8.0 g/dl