Chronic Lymphocytic Leukemia (CLL) Clinical Trials

• ≥18 years of age.

• Histologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) according to the 2018 international workshop (IW) CLL criteria who must have relapsed or be refractory to at least one prior therapy for CLL/SLL and require treatment by 2018 IWCLL criteria. In addition, lisaftoclax (600 mg) plus acalabrutinib combination cohort may include patients who are: (1) treatment-naïve, or (2) refractory to venetoclax.

• Eastern Cooperative Oncology Group (ECOG) ≤ 2.

• Patient must have objectively documented evidence of disease progression prior to study entry such as: escalating lymphocytes count with an increase \> 50% over a period of two months or doubling time in less than 6 months; enlarging adenopathy or splenomegaly; increasing cytopenias; clinical B symptoms -night sweats, fatigue, \> 1% weight loss in 6 months, fevers \> 100.50F for ≥ one month without infection.

• Adequate bone marrow function independent of growth factor:

∙ Absolute neutrophil count (ANC) ≥1.0× 109/L in patient without bone marrow involvement. This criterion does not apply to patients with bone marrow involvement by CLL/SLL.

‣ Platelets count ≥30 x 109/L (entry platelet count must be independent of transfusion within 7 days of first dose of lisaftoclax).

• Adequate renal and hepatic function as indicated by:

∙ Serum creatinine ≤1.5×upper limit of normal (ULN); if serum creatinine is \>1.5×ULN, creatinine clearance must be ≥ 50 mL/min, calculated using the Cockcroft and Gault formula(140-Age)x mas (kg)/(72x creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).

‣ Total bilirubin ≤1.5 x ULN, except patients with known Gilbert's syndrome.

‣ Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2.5 x ULN, Alkaline phosphatase\<2.5×ULN.

‣ International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT) ≤1.5×ULN unless the patient is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants.

• Females of childbearing potential (i.e., not postmenopausal for at least 2 years or surgically sterile) must have negative results for pregnancy test performed:

∙ At screening on a serum sample obtained within 14 days prior to the first lisaftoclax administration;

‣ Prior to dosing on a urine sample obtained on the first day of lisaftoclax administration, if it has been \>7 days since obtaining the serum pregnancy test results.

• Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing lisaftoclax:

∙ Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable;

‣ Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy

‣ Intrauterine device (IUD);

‣ Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal fellies or cream AND a condom);

‣ Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to lisaftoclax administration. If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to lisaftoclax administration.

• Male patients must refrain from sperm donation, from initial lisaftoclax administration until 90 days after the last dose of lisaftoclax.

⁃ Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).

⁃ Willingness and ability to comply with study procedures and follow-up examination.