Acalabrutinib in Combination With ACP-319, for Treatment of Chronic Lymphocytic Leukemia

Inclusion Criteria:

Men and women ≥ 18 years of age with a confirmed diagnosis of CLL, which has relapsed after, or been refractory to, ≥ 1 previous treatments for CLL; however, subjects with 17p deletion are eligible if they have relapsed after, or been refractory to, 1 prior treatment for CLL.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

Exclusion Criteria:

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 ≥ 2 years or which will not limit survival to < 2 years.
A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib and/or ACP-319, or put the study outcomes at undue risk.
Significant cardiovascular disease.
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.
Any immunotherapy within 4 weeks of first dose of study drug.
For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of CLL or other conditions. Note: Subjects may be using topical or inhaled corticosteroids as therapy for comorbid conditions.
Central nervous system (CNS) involvement by CLL.
Grade ≥ 2 toxicity (other than alopecia).
Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
Absolute neutrophil count (ANC) < 0.75 x 109/L or platelet count < 50 x 109/L unless due to disease involvement in the bone marrow.
Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.
Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc > 480 msec.